Biomedical subjects

P Visser

Publications and source records attributed to P Visser.

At least 19 recordsLinked to original sources

PubMed2005

In-hospital operative mortality of ruptured abdominal aortic aneurysm: a population-based analysis of 5593 patients in The Netherlands over a 10-year period.

OBJECTIVE: To determine the operative mortality of ruptured abdominal aortic aneurysm (RAAA) in The Netherlands. DESIGN: Retrospective population-based study of nation-wide in-hospital mortality of RAAA repair. METHODS: Data were obtained from a national registry for medical diagnosis and procedures. In-hospital mortality of RAAA repair, defined as death during hospital admission irrespective of the cause of death, was determined in the period 1991-2000. Variables of potential influence on in-hospital mortality, including age, gender, date of surgery and hospital type (0-399 beds, > or =400 beds or university hospitals) were studied in a multivariate analysis. RESULTS: The overall in-hospital mortality of RAAA repair in 5593 patients in the 10-year period was 41% (95% confidence interval: 40-42%). In the multivariate analysis, age and hospital type were the most important independent predictors for in-hospital mortality. Gender, year and season of surgery could not be identified as significant risk factors. CONCLUSIONS: Over a recent decade, in-hospital mortality of RAAA repair remained unchanged at 41%. Age and hospital class were the most important independent risk factors.

Age Factors↗

PubMed2004

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Aged↗

PubMed2001

Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes.

Genetic analysis in Drosophila suggests that Bicaudal-D functions in an essential microtubule-based transport pathway, together with cytoplasmic dynein and dynactin. However, the molecular mechanism underlying interactions of these proteins has remained elusive. We show here that a mammalian homologue of Bicaudal-D, BICD2, binds to the dynamitin subunit of dynactin. This interaction is confirmed by mass spectrometry, immunoprecipitation studies and in vitro binding assays. In interphase cells, BICD2 mainly localizes to the Golgi complex and has properties of a peripheral coat protein, yet it also co-localizes with dynactin at microtubule plus ends. Overexpression studies using green fluorescent protein-tagged forms of BICD2 verify its intracellular distribution and co-localization with dynactin, and indicate that the C-terminus of BICD2 is responsible for Golgi targeting. Overexpression of the N-terminal domain of BICD2 disrupts minus-end-directed organelle distribution and this portion of BICD2 co-precipitates with cytoplasmic dynein. Nocodazole treatment of cells results in an extensive BICD2-dynactin-dynein co-localization. Taken together, these data suggest that mammalian BICD2 plays a role in the dynein- dynactin interaction on the surface of membranous organelles, by associating with these complexes.

Animals↗

PubMed2001

Branching and differentiation defects in pulmonary epithelium with elevated Gata6 expression.

The transcription factor GATA6 is expressed in the fetal pulmonary epithelium of the developing mouse lung and loss of function studies strongly suggested that it is required for proper branching morphogenesis and epithelial differentiation. We have further investigated the role of GATA6 in this process by utilizing a pulmonary epithelium specific promoter to maintain high levels of GATA6 protein during fetal lung development. Transgenic mice expressing Gata6 cDNA under the control of the human Surfactant Protein-C (SP-C) promoter were generated and their lungs were analyzed during fetal stages. Transgenic lungs exhibit branching defects as early as embryonic day (E) 14.5 and molecular analysis just before birth (E18.5) shows a lack of distal epithelium differentiation whereas proximal epithelium is unaffected. Electron microscopic analysis and glycogen staining confirm the lack of differentiation to mature Type II cells. Thus, elevated levels of GATA6 protein affect early lung development and in analogy to other GATA factors in other tissues, GATA6 also plays a crucial role in the terminal differentiation in this case of the distal pulmonary epithelium.

Animals↗

PubMed2001

Irradiated versus nonirradiated endothelial cells: effect on proliferation of vascular smooth muscle cells.

PURPOSE: Endovascular radiation therapy is a promising strategy for the prevention of restenosis. Radiation prevents proliferation of vascular smooth muscle cells, thereby reducing the incidence of restenosis, but may also affect the remaining endothelial cells. For this reason, a comparison was made between irradiated and nonirradiated endothelial cells and their effects on the proliferation of vascular smooth muscle cells in a coculture system was evaluated. MATERIALS AND METHODS: A coculture system was used, in which both endothelial cells and vascular smooth muscle cells were grown on opposite sides of a semipermeable membrane. After a period of growth arrest, the proliferation of vascular smooth muscle cells was measured during four subsequent days. RESULTS: The presence of endothelial cells stimulated the proliferation of vascular smooth muscle cells during the first days of analysis but had an inhibitory effect during the subsequent days (P <.5). gamma-irradiation of endothelial cells resulted in a complete blockage of the proliferation of these cells. However, irradiated endothelial cells affected the proliferation of vascular smooth muscle cells in coculture in a fashion comparable to nonirradiated endothelial cells (P >.5). CONCLUSION: The results suggest that, in endovascular radiation therapy, irradiation of endothelial cells does not change their effects on the proliferative behavior of vascular smooth muscle cells.

Animals↗

PubMed2000

CFU-S(11) activity does not localize solely with the aorta in the aorta-gonad-mesonephros region.

The aorta-gonad-mesonephros (AGM) region is a potent hematopoietic site in the midgestation mouse conceptus and first contains colony-forming units-spleen day 11 (CFU-S(11)) at embryonic day 10 (E10). Because CFU-S(11) activity is present in the AGM region before the onset of hematopoietic stem cell (HSC) activity, CFU-S(11) activity in the complex developing vascular and urogenital regions of the AGM was localized. From E10 onward, CFU-S(11) activity is associated with the aortic vasculature, and is found also in the urogenital ridges (UGRs). Together with data obtained from organ explant cultures, in which up to a 16-fold increase in CFU-S(11) activity was observed, it was determined that CFU-S(11) can be increased autonomously both in vascular sites and in UGRs. Furthermore, CFU-S(11) activity is present in vitelline and umbilical vessels. This, together with the presence of CFU-S(11) in the UGRs 2 days before HSC activity, suggests both temporally and spatially distinct emergent sources of CFU-S(11). (Blood. 2000;96:2902-2904)

Animals↗

PubMed2000

A distal Schwann cell-specific enhancer mediates axonal regulation of the Oct-6 transcription factor during peripheral nerve development and regeneration.

The POU domain transcription factor Oct-6 is a major regulator of Schwann cell differentiation and myelination. During nerve development and regeneration, expression of Oct-6 is under the control of axonal signals. Identification of the cis-acting elements necessary for Oct-6 gene regulation is an important step in deciphering the complex signalling between Schwann cells and axons governing myelination. Here we show that a fragment distal to the Oct-6 gene, containing two DNase I-hypersensitive sites, acts as the Oct-6 Schwann cell-specific enhancer (SCE). The SCE is sufficient to drive spatially and temporally correct expression, during both normal peripheral nerve development and regeneration. We further demonstrate that a tagged version of Oct-6, driven by the SCE, rescues the peripheral nerve phenotype of Oct-6-deficient mice. Thus, our isolation and characterization of the Oct-6 SCE provides the first description of a cis-acting genetic element that responds to converging signalling pathways to drive myelination in the peripheral nervous system.

Animals↗

PubMed1999

Gp96/GRP94 is a putative high density lipoprotein-binding protein in liver.

We have previously shown that three high density lipoproteins (HDL)-binding proteins in liver, of 90, 110 and 180 kDa, are structurally related. In this study, these proteins are identified as gp96/GRP94. This protein is known to occur as a homodimer and has a dual subcellular localization: it is both an endoplasmic reticulum resident protein, where it is supposed to act as a chaperonin, and a plasma membrane protein, whose significance is unknown. In ultrastructural studies the plasma membrane localization of the homodimeric form was verified. The 90-kDa protein was abundantly present at the membranes of the endosomal/lysosomal vesicles as well as at the apical hepatocyte membranes, comprising the bile canaliculi. The monomeric protein is scarcely present at the basolateral membrane of the hepatocytes, but could be demonstrated in coated pits, suggesting involvement in receptor-mediated endocytosis. Labeling of the endoplasmic reticulum was virtually absent. Gp96/GRP94 was transiently expressed in COS-1 cells. However, the expressed protein was exclusively localized in the endoplasmic reticulum. Transfection with constructs in which the C-terminal KDEL sequence had been deleted, resulted in plasma membrane localized expression of protein, but only in an extremely low percentage of cells. In order to evaluate the HDL-binding capacities of this protein, stably transfected cells were generated, using several cell types. It appeared to be difficult to obtain a prolonged high level expression of gp96. In these cases, however, a marked increase of HDL-binding activity compared with the control cells could be observed.

Amino Acid Sequence↗

PubMed1999

Cell type-specific acquired protection from crystal adherence by renal tubule cells in culture.

BACKGROUND: Adherence of crystals to the surface of renal tubule epithelial cells is considered an important step in the development of nephrolithiasis. Previously, we demonstrated that functional monolayers formed by the renal tubule cell line, Madin-Darby canine kidney (MDCK), acquire protection against the adherence of calcium oxalate monohydrate crystals. We now examined whether this property is cell type specific. The susceptibility of the cells to crystal binding was further studied under different culture conditions. METHODS: Cell-type specificity and the influence of the growth substrate was tested by comparing calcium oxalate monohydrate crystal binding to LLC-PK1 cells and to two MDCK strains cultured on either permeable or impermeable supports. These cell lines are representative for the renal proximal tubule (LLC-PK1) and distal tubule/collecting duct (MDCK) segments of the nephron, in which crystals are expected to be absent and present, respectively. RESULTS: Whereas relatively large amounts of crystals adhered to subconfluent MDCK cultures, the level of crystal binding to confluent monolayers was reduced for both MDCK strains. On permeable supports, MDCK cells not only obtained a higher level of morphological differentiation, but also acquired a higher degree of protection than on impermeable surfaces. Crystals avidly adhered to LLC-PK1 cells, irrespective of their developmental stage or growth substrate used. CONCLUSIONS: These results show that the prevention of crystal binding is cell type specific and expressed only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK cells may mirror a specific functional characteristic of its in situ equivalent, the renal distal tubule/collecting ducts.

Animals↗

PubMed1999

Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II.

Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatment for this fatal disease, but the applicability of enzyme replacement therapy is under investigation. For this purpose, recombinant human acid alpha-glucosidase has been produced on an industrial scale in the milk of transgenic rabbits. In this paper we demonstrate the therapeutic effect of this enzyme in our knockout mouse model of GSDII. Full correction of acid alpha-glucosidase deficiency was obtained in all tissues except brain after a single dose of i.v. enzyme administration. Weekly enzyme infusions over a period of 6 months resulted in degradation of lysosomal glycogen in heart, skeletal and smooth muscle. The tissue morphology improved substantially despite the advanced state of disease at the start of treatment. The results have led to the start of a Phase II clinical trial of enzyme replacement therapy in patients.

Animals↗

PubMed1998

Comparison of sequence and function of the Oct-6 genes in zebrafish, chicken and mouse.

To examine the role of the Oct-6 gene in Schwann cell differentiation we have cloned and characterized the chicken and zebrafish homologues of the mouse Oct-6 gene. While highly homologous in the Pit1-Oct1/2-Unc86 (POU) domain, sequence similarities are limited outside this domain. Both genes are intronless and both proteins lack the amino acid repeats that are a characteristic feature of the mammalian Oct-6 proteins. However as in mammals, the aminoterminal parts of the chicken and zebrafish Oct-6 proteins are essential for transactivation of octamer containing promoters. By immunohistochemistry we have found that the chicken Oct-6 protein is expressed in late embryonic ensheathing Schwann cells of the sciatic nerve and is rapidly downregulated when myelination proceeds. This expression profile in glial cells is identical to that in the mouse and rat. Furthermore the zebrafish Oct-6 homolog is expressed in the posterior lateral nerve at a time when it contains actively myelinating Schwann cells. Thus despite extensive primary sequence divergence among the vertebrate Oct-6 proteins, the expression of the chicken and zebrafish Oct-6 proteins is consistent with the notion that Oct-6 functions as a 'competence factor' in promyelin cells to execute the myelination program.

Amino Acid Sequence↗

PubMed1998

A mouse model for the basal transcription/DNA repair syndrome trichothiodystrophy.

The sun-sensitive form of the severe neurodevelopmental, brittle hair disorder trichothiodystrophy (TTD) is caused by point mutations in the essential XPB and XPD helicase subunits of the dual functional DNA repair/basal transcription factor TFIIH. The phenotype is hypothesized to be in part derived from a nucleotide excision repair defect and in part from a subtle basal transcription deficiency accounting for the nonrepair TTD features. Using a novel gene-targeting strategy, we have mimicked the causative XPD point mutation of a TTD patient in the mouse. TTD mice reflect to a remarkable extent the human disorder, including brittle hair, developmental abnormalities, reduced life span, UV sensitivity, and skin abnormalities. The cutaneous symptoms are associated with reduced transcription of a skin-specific gene strongly supporting the concept of TTD as a human disease due to inborn defects in basal transcription and DNA repair.

Animals↗

PubMed1998

Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease.

Glycogen storage disease type II (GSDII; Pompe disease), caused by inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder affecting heart and skeletal muscles. A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa mRNA and have a virtually complete acid alpha-glucosidase deficiency. Glycogen-containing lysosomes are detected soon after birth in liver, heart and skeletal muscle cells. By 13 weeks of age, large focal deposits of glycogen have formed. Vacuolar spaces stain positive for acid phosphatase as a sign of lysosomal pathology. Both male and female knockout mice are fertile and can be intercrossed to produce progeny. The first born knockout mice are at present 9 months old. Overt clinical symptoms are still absent, but the heart is typically enlarged and the electrocardiogram is abnormal. The mouse model will help greatly to understand the pathogenic mechanism of GSDII and is a valuable instrument to explore the efficacy of different therapeutic interventions.

Animals↗

PubMed1997

Mechanisms for high methoxymorpholino doxorubicin cytotoxicity in doxorubicin-resistant tumor cell lines.

Methoxymorpholino doxorubicin (MMRDX) is an anthracycline analogue that is able to overcome tumor cell resistance to classical anthracyclines. Mechanisms for increased MMRDX cytotoxicity were analyzed in a small cell lung carcinoma cell line (GLC4), its 300-fold doxorubicin-resistant and multidrug resistance-associated protein (MRP)-over-expressing subline (GLC4/ADR), an ovarian carcinoma cell line (A2780) and its 100-fold doxorubicin resistant and P-glycoprotein (P-gp)-overexpressing subline A2780AD. Cross-resistance, measured with the MTT assay at MMRDX concentration resulting in 50% growth inhibition, was 1.8-fold in GLC4/ADR and 4.5-fold in A2780AD compared to their respective parental cell lines. Cellular MMRDX accumulation was equal in GLC4 and GLC4/ADR and 2-fold lower in A2780AD compared to A2780. Doxorubicin fluorescence was analyzed with confocal laser scan microscopy. Fluorescence was nuclear in sensitive, and cytoplasmic in resistant, cell lines, while MMRDX fluorescence was found in the nucleus in all cell lines. Pre-incubation with the MRP blocker MK 571 restored in GLC4/ADR cells the nuclear doxorubicin fluorescence pattern, as observed in GLC4 cells. MMRDX, thus, can largely overcome cross-resistance in these P-gp- and MRP-overexpressing doxorubicin-resistant cell lines. Our results suggest that MMRDX is not a substrate for MRP-mediated resistance.

Antibiotics, Antineoplastic↗

PubMed1997

Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation.

Transcription factor Sp1 has been implicated in the expression of many genes. Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures. We have inactivated the mouse Sp1 gene. Sp1-/- embryos are retarded in development, show a broad range of abnormalities, and die around day 11 of gestation. In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci. However, the expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/- embryos. MeCP2 is thought to be required for the maintenance of differentiated cells. We suggest that Sp1 is an important regulator of this process.

Animals↗

PubMed1997

Importance of a new tumor marker TRA-1-60 in the follow-up of patients with clinical stage I nonseminomatous testicular germ cell tumors.

BACKGROUND: TRA-1-60 is a new tumor marker for embryonal carcinoma-positive nonseminomatous testicular germ cell tumors (NSTGCT). Upper normal reference value (RV) and serum half-life (t1/2) were determined. The value was determined in the follow-up of 154 patients with stage I NSTGCT. METHODS: TRA-1-60 was measured in normal controls (n = 100) to determine RV and in patients without recurrence for t1/2. In all patients, TRA-1-60 was determined at the time of orchidectomy. In 42 patients with recurrence, values were also evaluated 1 month before and at the time of computed tomography-confirmed recurrence. Predictive values and survival probability were examined and compared with values for alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG). RESULTS: RV was 230 U/ml and t1/2 9.5 days. Elevated TRA-1-60 at the time of orchidectomy was not associated with recurrence. One month before recurrence, 21 of 42 patients had elevated TRA-1-60 levels (50%); 10 were negative for both AFP and hCG. At the time of recurrence, 24 patients had elevated TRA-1-60 levels (57.1%): 9 were negative for AFP/hCG. Patients with TRA-1-60 levels of > 500 U/ml had a poorer recurrence-free survival probability (p = 0.015). CONCLUSIONS: TRA-1-60 is useful in the follow-up of stage 1 NSTGCT. The combination of AFP, hCG, and TRA-1-60 may improve the early detection of recurrence.

Antigens, Neoplasm↗

PubMed1996

The POU factor Oct-6 and Schwann cell differentiation.

The POU transcription factor Oct-6, also known as SCIP or Tst-1, has been implicated as a major transcriptional regulator in Schwann cell differentiation. Microscopic and immunochemical analysis of sciatic nerves of Oct-6(-/-) mice at different stages of postnatal development reveals a delay in Schwann cell differentiation, with a transient arrest at the promyelination stage. Thus, Oct-6 appears to be required for the transition of promyelin cells to myelinating cells. Once these cells progress past this point, Oct-6 is no longer required, and myelination occurs normally.

Animals↗

PubMed1996

Increased urinary IgG/albumin index in normoalbuminuric insulin-dependent diabetic patients: a laboratory artefact.

The previous observation that urinary IgG excretion is increased in normoalbuminuric insulin-dependent (IDDM) patients is unexplained and could possibly be related to a laboratory phenomenon. When untreated urine samples were stored -20 degrees C for 2 to 4 weeks, the IgG/albumin Index (IgG clearance divided by albumin clearance) was higher in normoalbuminuric IDDM patients than in control subjects (0.91 (0.68-1.54), n = 27 vs 0.72 (0.55-0.79), n = 15 (median (interquartile range)), p < 0.05). In normo- and microalbuminuric IDDM patients the IgG/albumin index was higher in urine samples with glucose than without glucose (1.16 (0.93-1.68), n = 11 vs 0.73 (0.50-0.91), n = 16, p < 0.05, and 0.33 (0.23-0.60), n = 17 vs 0.15 (0.10-0.26), n = 14, p < 0.02 for normo- and microalbuminuric patients, respectively). We, therefore, evaluated the preserving effects of glucose and bovine serum albumin (BSA) on urinary IgG after 1 h to 16 weeks of freezing at -20 degrees C in 4 non-diabetic subjects (proteinuria ranging from 0.05 to 8.0 g 24 h-1). Urine samples were either stored without precautions or treated with addition of phosphate buffer, BSA (1%) and glucose 100 and 300 mM). The weekly decline from 1 to 16 weeks of IgG in the urine aliquots diluted 1:1 with buffered glucose 300 mM and glucose 300 mM + BSA 1% was insignificant, whereas urinary IgG declined with all other storage regimes (p < 0.05). These results suggest that glucose in urinary specimens of IDDM patients prevents at least in part the loss of urinary IgG and may thus explain the higher urinary IgG/albumin index when unprocessed urine is stored frozen before assay. Laboratory precautions are necessary when urinary IgG cannot be measured immediately.

Adult↗