188 research outputs found
Hereditary paragangliomas : clinical studies
In this thesis we describe the genetic, biochemical and clinical characteristics of patients with head and neck paragangliomas (HNPGL). In the Netherlands, the majority of SDHx mutation carriers, harbor a mutation in the SDHD gene. Twenty-nine percent of patients with HNPGL have increased urinary excretion of 3-methoxytyramine, indicating dopaminergic activity. Test sensitivity of plasma 3MT measurement equals the measurement of urinary deconjugated 3MT excretion. Only a minority of HNPGL patients have increased plasma chromogranin A levels. Therefore, the practical implications of the measurement of plasma chromogranin A levels are limited in HNPGL patients. Patients screened for pheochromocytomas, because of a hereditary predisposition, present with less signs and symptoms, lower urinary excretion rates of catecholamines, and smaller tumors than patients presenting with symptomatic pheochromocytomas. Despite these differences in biochemical activity and the sizes of the tumors, there is no difference in patients regarding peri-operative complications. Patients with bilateral carotid body tumors are at risk for developing sleep disordered breathing. Sleep disordered breathing is associated with increased carotid body output, which is reflected by increased chemosensitivity.UBL - phd migration 201
Study protocol: effect of infection, Modic and inflammation on clinical outcomes in surgery for radiculopathy (EIMICOR)
Background: Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of vertebral end plate pathology (Modic changes; MC) is associated with a negative effect on inflammation. It is hypothesized that in patients with MC, the (possibly bacterial induced) inflammation will be accompanied by pro inflammatory cytokines that worsen the outcome, and that in patients without MC, the inflammation is accompanied by cytokines that induce a resorption process to accelerate recovery.Methods: This prospective cohort study will include 160 lumbar and 160 cervical patients (total of 320), which are scheduled for surgery for either a lumbar or cervical herniated disc with ages between 18 and 75. The main and interaction effects of local bacterial infection (culture), inflammatory cells in disc material (immunohistology), MC (MRI), and blood biomarkers indicating inflammation or infection (blood sample evaluation) will be evaluated. Clinical parameters to be evaluated are leg pain on the 11 point NRS pain scale, Oswestry (lumbar spine) or Neck (cervical spine) Disability Index, Global Perceived Recovery, Womac Questionnaire, and medication status, at baseline, and after 6, 16, 26 and 52 weeks.Discussion: Gaining insight in the aetiology of pain and discomfort in radiculopathy caused by a herniated disc could lead to more effective management of patients. If the type of inflammatory cells shows to be of major influence on the rate of recovery, new immunomodulating treatment strategies can be developed to decrease the duration and intensity of symptoms. Moreover, identifying a beneficial inflammatory response in the disc through a biomarker in blood could lead to early identification of patients whose herniations will resorb spontaneously versus those that require surgery.OV
Longitudinal assessment of Alzheimer's beta-amyloid plaquedevelopment in transgenic mice monitored by in vivo magnetic resonance microimaging
Solid state NMR/Biophysical Organic Chemistr
The XMM-Newton serendipitous ultraviolet source survey catalogue
The XMM-Newton Serendipitous Ultraviolet Source Survey (XMM-SUSS) is a
catalogue of ultraviolet (UV) sources detected serendipitously by the Optical
Monitor (XMM-OM) on-board the XMM-Newton observatory. The catalogue contains
ultraviolet-detected sources collected from 2,417 XMM-OM observations in 1-6
broad band UV and optical filters, made between 24 February 2000 and 29 March
2007. The primary contents of the catalogue are source positions, magnitudes
and fluxes in 1 to 6 passbands, and these are accompanied by profile
diagnostics and variability statistics. The XMM-SUSS is populated by 753,578 UV
source detections above a 3 sigma signal-to-noise threshold limit which relate
to 624,049 unique objects. Taking account of substantial overlaps between
observations, the net sky area covered is 29-54 square degrees, depending on UV
filter. The magnitude distributions peak at 20.2, 20.9 and 21.2 in UVW2, UVM2
and UVW1 respectively. More than 10 per cent of sources have been visited more
than once using the same filter during XMM-Newton operation, and > 20 per cent
of sources are observed more than once per filter during an individual visit.
Consequently, the scope for science based on temporal source variability on
timescales of hours to years is broad. By comparison with other astrophysical
catalogues we test the accuracy of the source measurements and define the
nature of the serendipitous UV XMM-OM source sample. The distributions of
source colours in the UV and optical filters are shown together with the
expected loci of stars and galaxies, and indicate that sources which are
detected in multiple UV bands are predominantly star-forming galaxies and stars
of type G or earlier.Comment: Accepted for publication in MNRA
Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage
Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C>T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C>T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p
Bi-allelic <i>NIT1 </i>variants cause a brain small vessel disease characterized by movement disorders, massively dilated perivascular spaces, and intracerebral hemorrhage
Purpose: To describe a recessively inherited cerebral small vessel disease, caused by loss-of-function variants in Nitrilase1 (NIT1). Methods:We performed exome sequencing, brain magnetic resonance imaging, neuropathology, electron microscopy, western blotting, and transcriptomic and metabolic analyses in 7 NIT1-small vessel disease patients from 5 unrelated pedigrees. Results: The first identified patients were 3 siblings, compound heterozygous for the NIT1 c.727C>T; (p.Arg243Trp) variant and the NIT1 c.198_199del; p.(Ala68∗) variant. The 4 additional patients were single cases from 4 unrelated pedigrees and were all homozygous for the NIT1 c.727C>T; p.(Arg243Trp) variant. Patients presented in mid-adulthood with movement disorders. All patients had striking abnormalities on brain magnetic resonance imaging, with numerous and massively dilated basal ganglia perivascular spaces. Three patients had non-lobar intracerebral hemorrhage between age 45 and 60, which was fatal in 2 cases. Western blotting on patient fibroblasts showed absence of NIT1 protein, and metabolic analysis in urine confirmed loss of NIT1 enzymatic function. Brain autopsy revealed large electron-dense deposits in the vessel walls of small and medium sized cerebral arteries. Conclusion: NIT1-small vessel disease is a novel, autosomal recessively inherited cerebral small vessel disease characterized by a triad of movement disorders, massively dilated basal ganglia perivascular spaces, and intracerebral hemorrhage.</p
UV and EUV Instruments
We describe telescopes and instruments that were developed and used for
astronomical research in the ultraviolet (UV) and extreme ultraviolet (EUV)
regions of the electromagnetic spectrum. The wavelength ranges covered by these
bands are not uniquely defined. We use the following convention here: The EUV
and UV span the regions ~100-912 and 912-3000 Angstroem respectively. The
limitation between both ranges is a natural choice, because the hydrogen Lyman
absorption edge is located at 912 Angstroem. At smaller wavelengths,
astronomical sources are strongly absorbed by the interstellar medium. It also
marks a technical limit, because telescopes and instruments are of different
design. In the EUV range, the technology is strongly related to that utilized
in X-ray astronomy, while in the UV range the instruments in many cases have
their roots in optical astronomy. We will, therefore, describe the UV and EUV
instruments in appropriate conciseness and refer to the respective chapters of
this volume for more technical details.Comment: To appear in: Landolt-Boernstein, New Series VI/4A, Astronomy,
Astrophysics, and Cosmology; Instruments and Methods, ed. J.E. Truemper,
Springer-Verlag, Berlin, 201
Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy.
Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy in humans. However, despite knockout mice displaying a much more severe phenotype with premature death, bi-allelic variants in LDB3 have not yet been reported. Here we identify biallelic loss-of-function variants in five unrelated cardiomyopathy families by next-generation sequencing. In the first family, we identified compound heterozygous LOF variants in LDB3 in a fetus with bilateral talipes and mild left cardiac ventricular enlargement. Ultra-structural examination revealed highly irregular Z-disc formation, and RNA analysis demonstrated little/no expression of LDB3 protein with a functional C-terminal LIM domain in muscle tissue from the affected fetus. In a second family, a homozygous LDB3 nonsense variant was identified in a young girl with severe early-onset dilated cardiomyopathy with left ventricular non-compaction; the same homozygous nonsense variant was identified in a third unrelated female infant with dilated cardiomyopathy. We further identified homozygous LDB3 frameshift variants in two unrelated probands diagnosed with cardiomegaly and severely reduced left ventricular ejection fraction. Our findings demonstrate that recessive LDB3 variants can lead to an early-onset severe human phenotype of cardiomyopathy and myopathy, reminiscent of the knockout mouse phenotype, and supporting a loss of function mechanism
The Galaxy Evolution Explorer: A Space Ultraviolet Survey Mission
We give an overview of the Galaxy Evolution Explorer (GALEX), a NASA Explorer
Mission launched on April 28, 2003. GALEX is performing the first space UV
sky-survey, including imaging and grism surveys in two bands (1350-1750
Angstroms and 1750-2750 Angstroms). The surveys include an all-sky imaging
survey (m[AB] ~ 20.5), a medium imaging survey of 1000 square degrees (m[AB] ~
23), a deep imaging survey of 100 square degrees (m[AB] ~ 25), and a nearby
galaxy survey. Spectroscopic grism surveys (R=100-200) are underway with
various depths and sky coverage. Many targets overlap existing or planned
surveys. We will use the measured UV properties of local galaxies, along with
corollary observations, to calibrate the UV-global star formation rate
relationship in local galaxies. We will apply this calibration to distant
galaxies discovered in the deep imaging and spectroscopic surveys to map the
history of star formation in the universe over the redshift range 0 < z < 1.5,
and probe the physical drivers of star formation in galaxies. The GALEX mission
includes a Guest Investigator program supporting the wide variety of programs
made possible by the first UV sky survey.Comment: This paper will be published as part of the Galaxy Evolution Explorer
(GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of
papers will be available at http:/www.galex.caltech.edu/PUBLICATIONS/ after
November 22, 200
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