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D Fischer

Publications and source records attributed to D Fischer.

At least 37 records · Page 2Linked to original sources
PubMed2005

Characterisation of the promoter region of the human DNA-repair gene Rad51.

PURPOSE OF INVESTIGATION: Regulatory elements of the 5'-flanking region of the DNA-repair gene Rad51 were analysed to characterise pathological alterations of Rad51 mRNA expression during tumour development. METHODS: Various fragments of the Rad51 promoter were cloned into the pGL3 reporter vector and the respective promoter activity was determined by luciferase assays in transfected U2-OS cells. Transcription factor binding was identified using Protein/DNA arrays. RESULTS: The region encompassing base pairs -204 to -58 was identified as crucial for Rad51 gene transcription. Down regulator sequences are present upstream (-305 to -204) and downstream (-48 and +204) of this core promoter element. Promoter activity is significantly enhanced by substituting G at the polymorphic positions +135 and +172 for C and T, respectively. Transcription factors Ets1/PEA3, E2F1, p53, EGR1, and Stat5 were identified as relevant for regulating expression of Rad51. CONCLUSION: We identified three separate cis-sequence elements within the Rad51 transcriptional promoter, one ensuring basal levels of expression and two elements limiting expression to relatively low levels. The characterisation of transcription factor binding might help to explain high-level expression of Rad51 in a variety of solid tumours. The polymorphic sites appear important for the increased risk of breast and/or ovarian cancer for BRCA2 mutation carriers.

5' Flanking Region↗
PubMed2005

Clinical and histopathological aspects of central core disease associated and non-associated with RYR1 locus.

We analysed the clinical, histochemical, ultrastructural and genetic data of patients affected by central core disease (CCD) studied during the last 20 years. From a total series of 86 CCD-families, we have identified 46 CCD families with RYR1 mutations (16 autosomal dominant, 8 autosomal recessive, 17 sporadic cases and 5 de novo mutations). Out of the other 40 CCD families, the RyR1 gene was entirely excluded in 7 families, by cDNA sequencing or linkage analysis, indicating a genetic heterogeneity of CCD.

Humans↗
PubMed2004

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

BACKGROUND: Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. METHODS AND RESULTS: We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). CONCLUSION: These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.

Chronic Disease↗
PubMed2004

Breakup of H2 in singly ionizing collisions with fast protons: channel-selective low-energy electron spectra.

Dissociative as well as nondissociative single ionization of H2 by 6 MeV proton impact has been studied in a kinematically complete experiment by measuring the momentum vectors of the electron and the H+ fragment or the H+2 target ion, respectively. For the two ionization pathways, the electron spectra reveal the role of autoionization of the doubly and singly excited states of H2. The latter explicitly involve the coupling between the electronic and the nuclear motion of the molecule. This is a clear manifestation of a breakdown of the Born-Oppenheimer approximation.

Journal Article↗
PubMed2004

Poorly conserved ORFs in the genome of the archaea Halobacterium sp. NRC-1 correspond to expressed proteins.

MOTIVATION: A large fraction of open reading frames (ORFs) identified as 'hypothetical' proteins correspond to either 'conserved hypothetical' proteins, representing sequences homologous to ORFs of unknown function from other organisms, or to hypothetical proteins lacking any significant sequence similarity to other ORFs in the databases. Elucidating the functions and three-dimensional structures of such orphan ORFs, termed ORFans or poorly conserved ORFs (PCOs), is essential for understanding biodiversity. However, it has been claimed that many ORFans may not encode for expressed proteins. RESULTS: A genome-wide experimental study of 'paralogous PCOs' in the halophilic archaea Halobacterium sp. NRC-1 was conducted. Paralogous PCOs are ORFs with at least one homolog in the same organism, but with no clear homologs in other organisms. The results reveal that mRNA is synthesized for a majority of the Halobacterium sp. NRC-1 paralogous PCO families, including those comprising relatively short proteins, strongly suggesting that these Halobacterium sp. NRC-1 paralogous PCOs correspond to true, expressed proteins. Hence, further computational and experimental studies aimed at characterizing PCOs in this and other organisms are merited. Such efforts could shed light on PCOs' functions and origins, thereby serving to elucidate the vast diversity observed in the genetic material.

Bacterial Proteins↗
PubMed2004

[Isaacs' syndrome. Diagnosis and differential diagnosis of neuromyotonia].

Neuromyotonia is a clinical and electrophysiological syndrome of spontaneous muscle fiber activity due to hyperexcitability of peripheral nerve origin causing generalised, visible myokymia and muscular cramps. Electromyography shows abnormal doublet and triplet discharges of high intraburst frequency as well as myokymic and neuromyotonic discharges. Fasciculations and fibrillation potentials are common. Most commonly, neuromyotonia is an acquired immune-mediated disorder (Isaacs' syndrome) showing elevated antibody levels against presynaptic, voltage-gated, potassium channels. Some of these patients have additional autonomic (hyperhidrosis) and/or CNS symptoms similar to those from limbic encephalitis (referred to then as Morvan's syndrome). We report on a patient with Isaacs' syndrome and discuss the clinical and electrophysiological features, pathophysiology, diagnosis, and differential diagnosis of diseases with peripheral nerve hyperexcitability.

Diagnosis, Differential↗
PubMed2004

Wireless capsule video endoscopy compared to barium follow-through and computerised tomography in patients with suspected Crohn's disease--final report.

BACKGROUND: Wireless capsule endoscopy is a superior diagnostic tool to barium small bowel follow-through and enteroscopy in diagnosing patients with occult blood loss. AIM: To compare capsule endoscopy with barium follow-through and entero-computerised tomography in patients with suspected Crohn's disease. SUBJECTS AND METHODS: Thirty-five patients with suspected Crohn's disease underwent the three examinations. The radiologist and gastroenterologist were blinded to each other's results. In cases of discrepancy, colonoscopy and ileoscopy were performed. RESULTS: Thirty-five patients (22 males), mean age 28.4 years, were included. Eighty-eight percent had abdominal pain, 83% had diarrhoea and 69% had weight loss. The diagnostic yield of capsule endoscopy was 77% versus 23% and 20% of barium and computerised tomography examinations, respectively (P < 0.05). The capsule detected all of the lesions diagnosed by barium follow-through and entero-computerised tomography. CONCLUSIONS: Capsule endoscopy is a superior and more sensitive diagnostic tool than barium follow-through and entero-computerised tomography in patients with suspected Crohn's disease.

Adult↗
PubMed2004

[Neuroprotection and regeneration after traumatic lesion of the optic nerve].

BACKGROUND: After a traumatic lesion of the optic nerve, retinal ganglion cells (RGC) undergo massive degeneration by apoptosis, which leads to loss of vision in the affected eye. Like other neurones in the central nervous system, RGC are not able to regenerate their damaged axons spontaneously. We used special surgical methods and pharmacological measures to achieve enhanced survival and regeneration of damaged RGC. MATERIALS AND METHODS: Studies were performed using the model of RGC degeneration induced by severing the optic nerve of adult rats. RGC were loaded with a fluorescent dye, and several drugs were applied intravitreally. The effects were evaluated after two weeks by counting the surviving RGC. For regeneration studies, an autologous peripheral nerve graft was sutured to the stump of the cut optic nerve, or the ends of the cut optic nerve were re-sutured. Recovery of RGC function was assessed by VEP measurements. RESULTS: The number of RGC surviving an axotomy increased significantly after intravitreal injections of aurintricarboxylic acid, cortisol, a caspase inhibitor, brimonidine or microglia-targeted substances. Regeneration of cut axons was enhanced by aurintricarboxylic acid or cortisol. In addition, considerable neuroprotective and regenerative effects including partial restoration of VEP were induced by lens injury, which results in a gradual release of crystallins into the vitreous, or by intravitreal injection of purified crystallins. CONCLUSION: The loss of vision after an optic nerve trauma can be reduced in this animal model by suitable neuroprotective measures, which raises hope for the treatment of patients.

Animals↗
PubMed2003

Probing scattering wave functions close to the nucleus.

Recently, three-dimensional imaging of the ejected electrons following 100 MeV/amu C6+ single ionization of helium led to the observation of a new structure not predicted by theory [Nature (London) 422, 48 (2003)]]. Instead of the usual "recoil lobe" centered on the momentum-transfer axis, a ring-shaped structure centered on the beam axis was observed. New measurements at 2 MeV/amu exhibit a similar structure, which is now predicted by theory. We argue that the same theory failed at 100 MeV/amu because the faster projectiles probe distances much closer to the nucleus, where our multiple-scattering model is expected to break down.

Journal Article↗
PubMed2003

[Macrophagic myofasciitis: inflammatory, vaccination-associated muscular disease].

HISTORY AND ADMISSION FINDINGS: A 67-year-old man presented with a 6-week history of slowly progressive muscle pain and generalized muscular weakness. Neurological examination showed symmetrical proximal weakness (MRC grade 4/5). INVESTIGATIONS: Laboratory tests revealed an elevated CK level of 124 U/l (normal < 80). Needle EMG showed pathological spontaneous activity in proximal muscle groups. A diagnostic muscle biopsy taken from the left deltoid muscle revealed a characteristic infiltrate of PAS-positive and acid phosphatase-positive macrophages. Electron microscopic analysis of muscle tissue failed to demonstrate aluminium hydroxide inclusion. Serological analysis excluded antibodies against HAV and HBV but was compatible with a previous tetanus vaccination (antibody titre of 2.3 IE/ml). TREATMENT: A 2-year treatment with steroids and azathioprine led to complete recovery of muscle strength without relapse after discontinuing the immunosuppression. CONCLUSION: Macrophagic myofasciitis (MMF) is a rare inflammatory muscle disorder characterized by a characteristic infiltration of muscle tissue by PAS-positive macrophages, which is caused by pathological persistence of vaccine-derived aluminium hydroxide. The diagnosis can only be established by an open muscle biopsy from the muscle that was used for intramuscular vaccination.

Adrenal Cortex Hormones↗
PubMed2003

Rescattering of ultralow-energy electrons for single ionization of Ne in the tunneling regime.

Electron emission for single ionization of Ne by 25 fs, 1.0 PW/cm(2) laser pulses at 800 nm has been investigated in a kinematically complete experiment using a "reaction microscope." Mapping the complete final state momentum space with high resolution, a distinct local minimum is observed at P(e parallel )=0, where P(e parallel ) is the electron momentum parallel to the laser polarization. Whereas tunneling theory predicts a maximum at zero momentum, our findings are in good agreement with recent semiclassical predictions which were interpreted to be due to "recollision."

Journal Article↗
PubMed2003

Projectile-charge sign dependence of four-particle dynamics in helium double ionization.

Double ionization of helium by 6 MeV proton impact has been explored in a kinematically complete experiment using a "reaction microscope." For the first time, fully differential cross sections for positively charged projectiles have been obtained and compared with data from 2 keV electron impact. The significant differences observed in the angular distribution of the ejected electrons are attributed to the charge sign of the projectile, resulting in different dynamics of the four-particle Coulomb system, which is not considered in the first Born approximation.

Journal Article↗
PubMed2003

Three-dimensional imaging of atomic four-body processes.

To understand the physical processes that occur in nature we need to obtain a solid concept about the 'fundamental' forces acting between pairs of elementary particles. It is also necessary to describe the temporal and spatial evolution of many mutually interacting particles under the influence of these forces. This latter step, known as the few-body problem, remains an important unsolved problem in physics. Experiments involving atomic collisions represent a useful testing ground for studying the few-body problem. For the single ionization of a helium atom by charged particle impact, kinematically complete experiments have been performed since 1969 (ref. 7). The theoretical analysis of such experiments was thought to yield a complete picture of the basic features of the collision process, at least for large collision energies. These conclusions are, however, almost exclusively based on studies of restricted electron-emission geometries. Here, we report three-dimensional images of the complete electron emission pattern for the single ionization of helium by the impact of C6+ ions of energy 100 MeV per a.m.u. (a four-body system) and observe features that have not been predicted by any published theoretical model. We propose a higher-order ionization mechanism, involving the interaction between the projectile and the target nucleus, to explain these features.

Journal Article↗
PubMed2003

Intranasal immunization of guinea pigs with an immunodominant foot-and-mouth disease virus peptide conjugate induces mucosal and humoral antibodies and protection against challenge.

Guinea pigs immunized intranasally with a keyhole limpet hemocyanin-linked peptide, corresponding to the prominent G-H loop of the VP1 protein of foot-and-mouth disease virus, raised substantial levels of antipeptide and virus-neutralizing antibodies in sera and of peptide-specific secretory immunoglobulin A in nasal secretions. In groups of animals immunized intranasally without adjuvant, 86 percent were fully protected upon challenge with homotypic virus. Surprisingly, animals given the peptide conjugates plus the mucosal adjuvant cholera toxin were afforded only partial protection in that primary lesions were observed in most animals, although spread to other feet was prevented. These results indicate that intranasal inoculation with the peptide offers a potential route of vaccination against foot-and-mouth disease and may be useful for eliciting protection in the upper respiratory tracts of susceptible animals.

Administration, Intranasal↗