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Biomedical subjects

A Janssens

Publications and source records attributed to A Janssens.

At least 19 recordsLinked to original sources

Polar domains in lead titanate films under tensile strain.

Thin films of PbTiO3, a classical ferroelectric, have been grown under tensile strain on single-crystal substrates of DyScO3. The films, of only 5 nm thickness, grow fully coherent with the substrate, as evidenced by synchrotron x-ray diffraction. A mapping of the reciprocal space reveals intensity modulations (satellites) due to regularly spaced polar domains in which the polarization appears rotated away from the substrate normal, characterizing a low-symmetry phase not observed in the bulk material. This could have important practical implications since these phases are known to be responsible for ultrahigh piezoelectric responses in complex systems.

Journal Article↗

Regulatory aspects of radiation protection.

The paper introduces the projects launched by the European Community to foster prospects in dosimetry, radiation protection and best use of equipment in the medical field. These projects are put in perspective with the European legal framework for radiation protection, in particular, the Basic Safety Standards Directive, the Medical Exposures Directive and the Directive on High-Activity Sealed Sources. A summary is given of the overall mission statements of the commission services in the field of radiation protection, including the field of research, and how they relate to other actions in the overall health policy of the EU. In conclusion, a number of priority areas for future work in the medical field are highlighted.

European Union↗

Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium.

TRPV4 is a broadly expressed Ca2+-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. TRPV4 gates in response to a large variety of stimuli, including cell swelling, warm temperatures, the synthetic phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), and the endogenous lipid arachidonic acid (AA). Activation by cell swelling and AA requires cytochrome P450 (CYP) epoxygenase activity to convert AA to epoxyeicosatrienoic acids (EETs) such as 5,6-EET, 8,9-EET, which both act as direct TRPV4 agonists. To evaluate the role of TRPV4 and its modulation by the CYP pathway in vascular endothelial cells, we performed Ca2+ imaging and patch-clamp measurements on mouse aortic endothelial cells (MAECs) isolated from wild-type and TRPV4(-/-) mice. All TRPV4-activating stimuli induced robust Ca2+ responses in wild-type MAECs but not in MAECs isolated from TRPV4(-/-) mice. Upregulation of CYP2C expression by preincubation with nifedipine enhanced the responses to AA and cell swelling in wild-type MAECs, whereas responses to other stimuli remained unaffected. Conversely, inhibition of CYP2C9 activity with sulfaphenazole abolished the responses to AA and hypotonic solution (HTS). Moreover, suppression of EET hydrolysis using 1-adamantyl-3-cyclo-hexylurea or indomethacin, inhibitors of soluble epoxide hydrolases (sEHs), and cyclooxygenases, respectively, enhanced the TRPV4-dependent responses to AA, HTS, and EETs but not those to 4alpha-PDD or heat. Together, our data establish that CYP-derived EETs modulate the activity of TRPV4 channels in endothelial cells and shows the unraveling of novel modulatory pathways via CYP2C modulation and sEH inhibition.

8,11,14-Eicosatrienoic Acid↗

Results of the European Commission Marina II study: part II--effects of discharges of naturally occurring radioactive material.

Enhanced levels of naturally occurring radioactive materials (NORM) are produced through various industrial operations and may lead to discharges to the marine environment. A recent study, called MARINA II, carried out for the European Commission considered discharges of radionuclides from the NORM industries to north European marine waters and their consequences. There are two main sources that were considered in the study. The use of phosphogypsum during the production of phosphoric acid by the fertiliser industry and the pumping of oil and gas from the continental shelf in the North Sea which produces large quantities of water contaminated with enhanced levels of naturally occurring radionuclides. Discharges of alpha emitting radionuclides from these two industries have contributed significantly to the total input of alpha emitters to north European waters over the period 1981-2000 (data were not available prior to 1981). Discharges due to the use of phosphogypsum have declined since the early 1990s and are now very low. Discharges from the oil and gas industries stabilised in the second half of the 1990s and are now the major contributor to alpha discharges to the region. As most European countries do not report discharges of radioactivity with the water produced during extraction, there is considerable uncertainty in the discharges used in the study. The impact of the discharges has been estimated both in terms of the effect on non-human biota and the radiological impact for people. In the 1980s the radiation dose rates to marine biota in the region around a phosphate plant on the north-west coast of England were as high due to the discharges from the phosphate plant as those near to the Sellafield reprocessing plant due to its discharges. In recent years the additional dose to marine biota in this region due to the past NORM discharges is of the same order of magnitude as the natural background. The collective dose rate was estimated to determine the radiological impact on people. The peak collective dose rate from the NORM industries occurred in 1984 and was just over 600 manSv y(-1). The collective dose rate fell with time as discharges from the phosphate industry reduced and was estimated as under 200 manSv y(-1) in 2000.

Chemical Industry↗

Results of the European Commission MARINA II study: part I--general information and effects of discharges by the nuclear industry.

From the collated data relevant to discharges by the nuclear industry, it results that the input of beta activity (excluding Chernobyl fallout and tritium) into the OSPAR region decreased by a factor of 4 from 1986 to 1991, reaching by this date the same level as in the early 1950s. Over the same period the discharges of the alpha activity into the OSPAR region also decreased by a factor 3, the same trend has been seen also for tritium. Since 1986 the effective dose to members of the critical group in the vicinity of Sellafield and Cap de La Hague was consistently below the ICRP and EU limit of 1 mSv per year to members of the general public. The overall radiological impact from nuclear industry on the population of the European Union from the OSPAR area has decreased from 280 manSv y(-1) in 1978 to 14 manSv y(-1) in 2000.

Environmental Monitoring↗

Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4.

TRPV4 is a Ca(2+)- and Mg(2+)-permeable cation channel within the vanilloid receptor subgroup of the transient receptor potential (TRP) family, and it has been implicated in Ca(2+)-dependent signal transduction in several tissues, including brain and vascular endothelium. TRPV4-activating stimuli include osmotic cell swelling, heat, phorbol ester compounds, and 5',6'-epoxyeicosatrienoic acid, a cytochrome p450 epoxygenase metabolite of arachidonic acid (AA). It is presently unknown how these distinct activators converge on opening of the channel. Here, we demonstrate that blockers of phospholipase A(2) (PLA(2)) and cytochrome p450 epoxygenase inhibit activation of TRPV4 by osmotic cell swelling but not by heat and 4alpha-phorbol 12,13-didecanoate. Mutating a tyrosine residue (Tyr-555) in the N-terminal part of the third transmembrane domain to an alanine strongly impairs activation of TRPV4 by 4alpha-phorbol 12,13-didecanoate and heat but has no effect on activation by cell swelling or AA. We conclude that TRPV4-activating stimuli promote channel opening by means of distinct pathways. Cell swelling activates TRPV4 by means of the PLA(2)-dependent formation of AA, and its subsequent metabolization to 5',6'-epoxyeicosatrienoic acid by means of a cytochrome p450 epoxygenase-dependent pathway. Phorbol esters and heat operate by means of a distinct, PLA(2)- and cytochrome p450 epoxygenase-independent pathway, which critically depends on an aromatic residue at the N terminus of the third transmembrane domain.

Animals↗

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia.

MLLT10 (previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-year-old male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3' of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3'MLLT10followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL.

Acute Disease↗

Aspartate residues of the Glu-Glu-Asp-Asp (EEDD) pore locus control selectivity and permeation of the T-type Ca(2+) channel alpha(1G).

The structural determinant of the permeation and selectivity properties of high voltage-activated (HVA) Ca(2+) channels is a locus formed by four glutamate residues (EEEE), one in each P-region of the domains I-IV of the alpha(1) subunit. We tested whether the divergent aspartate residues of the EEDD locus of low voltage-activated (LVA or T-type) Ca(2+) channels account for the distinctive permeation and selectivity features of these channels. Using the whole-cell patch-clamp technique in the HEK293 expression system, we studied the properties of the alpha(1G) T-type, the alpha(1C) L-type Ca(2+) channel subunits, and alpha(1G) pore mutants, containing aspartate-to-glutamate conversions in domain III, domain IV, or both. Three characteristic features of HVA Ca(2+) channel permeation, i.e. (a) Ba(2+) over Ca(2+) permeability, (b) Ca(2+)/Ba(2+) anomalous mole fraction effect (AMFE), and (c) high Cd(2+) sensitivity, were conferred on the domain III mutant (EEED) of alpha(1G). In contrast, the relative Ca(2+)/Ba(2+) permeability and the lack of AMFE of the alpha(1G) wild type channel were retained in the domain IV mutant (EEDE). The double mutant (EEEE) displayed AMFE and a Cd(2+) sensitivity similar to that of alpha(1C), but currents were larger in Ca(2+)- than in Ba(2+)-containing solutions. The mutation in domain III, but not that in domain IV, consistently displayed outward fluxes of monovalent cations. H(+) blocked Ca(2+) currents in all mutants more efficiently than in alpha(1G). In addition, activation curves of all mutants were displaced to more positive voltages and had a larger slope factor than in alpha(1G) wild type. We conclude that the aspartate residues of the EEDD locus of the alpha(1G) Ca(2+) channel subunit not only control its permeation properties, but also affect its activation curve. The mutation of both divergent aspartates only partially confers HVA channel permeation properties to the alpha(1G) Ca(2+) channel subunit.

Aspartic Acid↗

Molecular cytogenetic and clinical findings in ETV6/ABL1-positive leukemia.

Rearrangements of 12p, resulting from deletions or translocations, are common findings in hematologic malignancies. In many cases, these rearrangements target the ETV6 gene (previously called TEL) located at 12p13. Various partner genes have been implicated in the formation of fusion genes with ETV6. These include PDGFRB, JAK2, NTRK3, ABL2, and ABL1, each of which encodes for proteins with tyrosine kinase activity. To date, ETV6/ABL1 transcripts have been detected in only four patients with a leukemic disorder. Here, we describe one adult with chronic myeloid leukemia and a child with T-cell acute lymphocytic leukemia with ETV6/ABL1. Molecular cytogenetic analysis confirmed that formation of an ETV6/ABL1 fusion in these patients required at least three chromosomal breaks and showed that each of these translocations is the result of a complex chromosomal rearrangement. Molecular analysis showed the presence of two fusion transcripts in both patients as the result of alternative splicing, questioning the suggested role of these transcripts in the lineage specificity. Clinical findings of these patients were compared to those of previously reported cases, and the possible clinical and biological similarities between ETV6/ABL1 and other fusion genes leading to increased tyrosine kinase activity are discussed.

Child, Preschool↗

Pyoderma gangrenosum as an early revelator of acute leukemia.

Bullous pyoderma gangrenosum is an atypical, more superficial variety of the classical pyoderma and is often associated with myeloproliferative disorders. We present the case of a patient who presented initially with subcutaneous nodules and who developed bullous lesions afterwards. Histological evaluation showed the presence of neutrophilic infiltrates in both lesions. A few months after the diagnosis of bullous pyoderma gangrenosum, an underlying leukemia was revealed. Our case illustrates the importance of regular blood and bone marrow examinations in patients with atypical bullous pyoderma gangrenosum, resulting in a rapid diagnosis of the underlying disease.

Female↗

Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis.

Neutrophils (PMNs) from patients with secondary iron overload have an increased iron and ferritin content as well as a phagocytosis defect. Several serum components might be incriminated in the cellular iron accumulation. We therefore compared the effects on the PMN phagocytosis of total serum as well as the ferritin and transferrin fractions of serum derived from patients with thalassemia major and healthy control subjects. An incubation system of PMNs was developed. PMN phagocytosis was measured before and after incubation. Total serum from patients with thalassemia induced a defect that was prevented by co-incubation with deferoxamine (DFO). Gel-filtration chromatography was performed to separate the serum fraction containing transferrin and albumin from that containing ferritin. The transferrin-albumin fraction had no effect on PMN phagocytosis. On the contrary, the ferritin fraction of normal serum was deleterious to PMN phagocytosis, and the same fraction from thalassemic serum decreased PMN phagocytosis even more. Co-incubation with DFO or catalase improved this defect. Moreover, a cellular increase in the L-type subunit of ferritin was observed after the incubation of PMNs with the ferritin-containing fraction from thalassemic serum. In conclusion, serum from patients with thalassemia is toxic to PMNs, and this toxicity is due to ferritin-associated iron.

Adolescent↗

Erythromelalgia: a clue to the diagnosis of polycythemia vera.

We report the case of a 74-year-old woman with recurrent episodes of symmetrical congestion and erythema in the distal lower legs causing a burning distress. Laboratory and clinical investigations revealed an underlying myeloproliferative disorder. The cutaneous symptoms were atypical of erythromelalgia. Salicylates and treatment of the underlying polycythemia were able to eliminate the skin lesions but not entirely suppress the subjective discomfort.

Aged↗

[The milking machine as a cause of severe agitation in cows (and the farmer) during milking].

A dairy farmer had complaints about uneasiness of the cows during milking. The problems started after changing some parts of the milking machine. Therefore a dynamic milking machine test was carried out to detect the cause of the problems. This test showed that the drainage ability of the milking machine was insufficient in cows with a high milkability (> 4.0 kg/min). The cyclic variations in the short milk tube and the drop of the mean vacuum in the short milk tube did not comply with the standards in cows with a high milkability. Moreover, in these cows, the mean vacuum in the beginning of the long milk tube was too low. Beside, the vacuum in the mouthpiece of the teat cup liner in cows with small teats was far above the standards and the shut off valves in the claws, which must lock the exit to the long milk tube nipple when the cluster is taken off automatically, did not function anymore. The way these deviations disturbed the milking procedure, is discussed. The farmer was advised (i) to replace the automatic cluster remover system by an electronically controlled one. (ii) and to replace the milking claws by claws with a larger volume (iii) and to replace the teat cup liners by teat cup liners with a smaller diameter. After the implementations of all advises, the cows were at ease again.

Animals↗

Anticardiolipin antibodies (ACA) are most often not associated with lupus-like anticoagulant (LLAC) in human immunodeficiency virus (HIV) infection.

Anticardiolipin antibodies (ACA) and lupus-like anticoagulant (LLAC) have been studied in a group of 142 non-hospitalized and a group of 72 hospitalized HIV infected patients. We observed a variable frequency of ACA positivity ranging from 7.7% to 30.3% according to the groups of patients and the isotype of immunoglobulin fraction containing ACA activity. None of the patients investigated presented a prolongation of the activated partial thromboplastin time (APTT) compatible with the presence of a LLAC. Some patients presented a weak anticoagulant activity only detected by the tissue thromboplastin inhibition (TTI) test. No positive correlation was found between this latter test and ACA. We conclude that, like in syphilitic patients, ACA present in HIV infected patients are most often not associated with LLAC.

Antibodies↗