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Biomedical subjects

M Hauser

Publications and source records attributed to M Hauser.

At least 19 recordsLinked to original sources

HESS observations of the galactic center region and their possible dark matter interpretation.

The detection of gamma rays from the source HESS J1745-290 in the Galactic Center (GC) region with the High Energy Spectroscopic System (HESS) array of Cherenkov telescopes in 2004 is presented. After subtraction of the diffuse gamma-ray emission from the GC ridge, the source is compatible with a point source with spatial extent less than 1.2;{'}(stat) (95% C.L.). The measured energy spectrum above 160 GeV is compatible with a power law with photon index of 2.25+/-0.04(stat)+/-0.10(syst) and no significant flux variation is detected. It is finally found that the bulk of the very high energy emission must have non-dark-matter origin.

Journal Article↗

Fast variability of tera-electron volt gamma rays from the radio galaxy M87.

The detection of fast variations of the tera-electron volt (TeV) (10(12) eV) gamma-ray flux, on time scales of days, from the nearby radio galaxy M87 is reported. These variations are about 10 times as fast as those observed in any other wave band and imply a very compact emission region with a dimension similar to the Schwarzschild radius of the central black hole. We thus can exclude several other sites and processes of the gamma-ray production. The observations confirm that TeV gamma rays are emitted by extragalactic sources other than blazars, where jets are not relativistically beamed toward the observer.

Journal Article↗

Myocardial scars determined by delayed-enhancement magnetic resonance imaging and positron emission tomography are not common in right ventricles with systemic function in long-term follow up.

OBJECTIVE: To test the hypothesis that myocardial scars are common in patients with systemic right ventricles. METHODS: 27 consecutive patients with systemic right ventricle were studied with delayed-enhancement magnetic resonance imaging and positron emission tomography. Of the 27 patients, 18 had had an atrial switch operation a mean of 21.8 (SD 4.5) years previously and were 23.4 (SD 5.3) years old. Nine patients without previous heart surgery had congenitally corrected transposition of the great arteries and were 35.3 (SD 15.6) years old. RESULTS: Only one patient had a subendocardial scar identified by delayed-enhancement magnetic resonance imaging. Positron emission tomography identified no myocardial scars. CONCLUSIONS: This study shows that the hypothesis that myocardial scars are common in patients with systemic right ventricles is not correct.

Adolescent↗

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA.

We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-gamma ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination.

Adult↗

A low level of extragalactic background light as revealed by gamma-rays from blazars.

The diffuse extragalactic background light consists of the sum of the starlight emitted by galaxies through the history of the Universe, and it could also have an important contribution from the 'first stars', which may have formed before galaxy formation began. Direct measurements are difficult and not yet conclusive, owing to the large uncertainties caused by the bright foreground emission associated with zodiacal light. An alternative approach is to study the absorption features imprinted on the gamma-ray spectra of distant extragalactic objects by interactions of those photons with the background light photons. Here we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and 1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their unexpectedly hard spectra provide an upper limit on the background light at optical/near-infrared wavelengths that appears to be very close to the lower limit given by the integrated light of resolved galaxies. The background flux at these wavelengths accordingly seems to be strongly dominated by the direct starlight from galaxies, thus excluding a large contribution from other sources-in particular from the first stars formed. This result also indicates that intergalactic space is more transparent to gamma-rays than previously thought.

Journal Article↗

Discovery of very-high-energy gamma-rays from the Galactic Centre ridge.

The source of Galactic cosmic rays (with energies up to 10(15) eV) remains unclear, although it is widely believed that they originate in the shock waves of expanding supernova remnants. At present the best way to investigate their acceleration and propagation is by observing the gamma-rays produced when cosmic rays interact with interstellar gas. Here we report observations of an extended region of very-high-energy (> 10(11) eV) gamma-ray emission correlated spatially with a complex of giant molecular clouds in the central 200 parsecs of the Milky Way. The hardness of the gamma-ray spectrum and the conditions in those molecular clouds indicate that the cosmic rays giving rise to the gamma-rays are likely to be protons and nuclei rather than electrons. The energy associated with the cosmic rays could have come from a single supernova explosion around 10(4) years ago.

Journal Article↗

ThPTR2, a di/tri-peptide transporter gene from Trichoderma harzianum.

The generation of a wide ESTs library and database from Trichoderma harzianum CECT 2413 was the base for identifying the gene ThPTR2, coding for a PTR family di/tri-peptide transporter. The deduced protein sequence of the ThPTR2 gene showed the conserved motifs and also the 12 transmembrane domains typical of the PTR transporters. The highest level of ThPTR2 expression was found when the fungus was grown in chitin as sole carbon source. We also found that ThPTR2 expression was increased when Trichoderma interacted directly in solid medium with the plant-pathogenic fungus Botrytis cinerea, showing that ThPTR2 is involved in the mycoparasitic process. Additionally, its expression was triggered by nitrogen starvation and a higher level of expression was also found when Trichoderma was grown in secondary nitrogen sources like allantoin, yeast extract, and urea. However, no difference was found when Trichoderma was grown in presence or absence of glucose as carbon source. Strain T34-15, a transformant that overexpressed the ThPTR2 gene, showed about a 2-fold increase in the uptake of the dipeptide Leu-Leu. Additionally, two transformants from the strain Trichoderma longibrachiatum T52 that overexpressed ThPTR2 were also studied, confirming the role of this gene in peptide transport. Other homologous genes to ThPTR2 were identified in other Trichoderma strains. ThPTR2 is the first experimentally confirmed PTR family transporter gene from filamentous fungi.

Amino Acid Motifs↗

Right heart failure due to an unroofed coronary sinus in an adult.

An unroofed coronary sinus is a rare congenital malformation with a strong association to a persistent left vena cava superior. In most cases it occurs together with complex cardiac anomalies such as left isomerism. We report on a 72-year-old man with clinical signs of right heart failure caused by an isolated unroofed coronary sinus: The diagnosis was made by means of transesophageal echocardiography with contrast injection.

Aged↗

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients.

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.

Aged↗

Discovery of very high energy gamma rays associated with an x-ray binary.

X-ray binaries are composed of a normal star in orbit around a neutron star or stellar-mass black hole. Radio and x-ray observations have led to the presumption that some x-ray binaries called microquasars behave as scaled-down active galactic nuclei. Microquasars have resolved radio emission that is thought to arise from a relativistic outflow akin to active galactic nuclei jets, in which particles can be accelerated to large energies. Very high energy gamma-rays produced by the interactions of these particles have been observed from several active galactic nuclei. Using the High Energy Stereoscopic System, we find evidence for gamma-ray emission of >100 gigaelectron volts from a candidate microquasar, LS 5039, showing that particles are also accelerated to very high energies in these systems.

Journal Article↗

A new population of very high energy gamma-ray sources in the Milky Way.

Very high energy gamma-rays probe the long-standing mystery of the origin of cosmic rays. Produced in the interactions of accelerated particles in astrophysical objects, they can be used to image cosmic particle accelerators. A first sensitive survey of the inner part of the Milky Way with the High Energy Stereoscopic System (HESS) reveals a population of eight previously unknown firmly detected sources of very high energy gamma-rays. At least two have no known radio or x-ray counterpart and may be representative of a new class of "dark" nucleonic cosmic ray sources.

Journal Article↗

Monitoring cytosolic pH of carboxysome-deficient cells of Synechocystis sp. PCC 6803 using fluorescence analysis.

Disruption of the ccmM gene in the cyanobacterium Synechocystis sp. PCC 6803 causes a deficiency of carboxysomes and impairs growth in ambient CO2. The effect of this gene defect on cellular metabolism was investigated using electron microscopy, biochemical and fluorescence analysis. Mutant cells were devoid of the characteristic dense polyhedral bodies called carboxysomes. The photosynthetic oxygen evolution was considerably lower in mutant cells compared to wild type, while Rubisco activity in cell extracts was similar. During photosynthetic CO2-dependent oxygen evolution, Rubisco Vmax dropped from 142 micromol mg-1 chlorophyll h-1 (WT) to 77 micromol mg-1 chlorophyll h-1 in the mutant cells, and the Km for Ci (inorganic carbon) increased from 0.5 mM (WT) to 40 mM. The fluorescent indicator, acridine yellow, was used for non-invasive measurements of cytoplasmic pH changes in whole cells induced by addition of Ci, making use of the decrease in fluorescence yield that accompanies cytoplasmic acidification. The experimental results indicate that control of the cytoplasmic pH is linked to the internal carbon pool (Ci). Both wild-type and ccmM-deficient cells showed a linear response of acridine yellow fluorescence quenching and, thus, of internal acidification, with respect to externally added inorganic carbon. However, the fluorescence analysis of mutant (carboxysome-free) cells indicated slower kinetics of Ci accumulation.

Carbon Dioxide↗

High-energy particle acceleration in the shell of a supernova remnant.

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.

Journal Article↗

Myocardial blood flow and coronary flow reserve in children with "normal" epicardial coronary arteries after the onset of Kawasaki disease assessed by positron emission tomography.

Myocardial blood flow (MBF) was investigated in children (14.2 +/- 5.01 years) with "resolved" coronary involvement after the onset of Kawasaki disease and angiographically normal epicardial coronary arteries. Ten asymptomatic children with a history of Kawasaki disease had electrocardiography, echocardiography, and positron emission tomography (PET) 10.3 +/- 6.01 years after onset of the acute illness. Myocardial perfusion was assessed by NH(3)- PET at rest and after vasodilatation and compared with that of 10 healthy volunteers (26.1 +/- 6.3 years). No patient had signs of myocardial ischemia; on echocardiography ventricular function was normal without dyskinetic areas or signs of enlargement or stenosis of the proximal coronary arteries. There was no statistical significant difference between patients and volunteers in MBF at rest (0.86 +/- 0.27 vs 0.77 +/- 0.17 ml/g/min), whereas MBF after vasodilatation (2.42 +/- 0.81 vs 3.10 +/- 0.8 ml/g/min) and coronary flow reserve (CFR) (2.89 +/- 0.26 vs 4.09 +/- 1.01 mmHg/ml/g/min) were significantly attenuated in the Kawasaki group. No stress-induced perfusion defects could be detected. In children with a history of Kawasaki disease and angiographically normal epicardial coronary arteries, there is a significant attenuation of MBF after vasodilatation and a significant reduction of CFR. Impairment of vasoreactive ability may indicate residual damage of the coronary arteries and may be a risk factor for atherosclerosis in adulthood.

Adenosine↗

Impaired left ventricular function after arterial switch operation: exclusion of significant coronary artery stenosis with an intravascular Doppler guidewire.

Patients after arterial switch operation for transposition of the great arteries are at risk for coronary artery stenosis or obstruction due to intraoperative manipulation. This case describes an infant with impaired left ventricular function 8 months after arterial switch operation. A hemodynamically significant left coronary artery stenosis was excluded by determination of coronary flow reserve using an intravascular Doppler guidewire.

Cardiac Surgical Procedures↗

Myocardial perfusion and coronary flow reserve assessed by positron emission tomography in patients after Fontan-like operations.

Ventricular dysfunction in patients after Fontan-like operations (FLOs) is a serious complication that might contribute to poor long-term results. Ischemic heart disease will have debilitating consequences on a Fontan heart. Ten patients (15.8 +/- 5.01 years) after FLO had transesophageal echocardiography and cardiac catheterization 9.3 +/- 4.2 years after surgery. Myocardial perfusion was assessed by NH3-positron emission tomography (rest/adenosine) and compared with that of 10 healthy adults (26.1 +/- 6.3 years). Ventricular function was normal in 4 and reduced in 6 patients; end systolic and end diastolic meridional wall stress was significantly elevated in the FLO group. Coronary angiography revealed no stenosis of the coronaries. Compared to normals, myocardial blood flow (MBF) at rest was higher in the FLO group (0.99 +/- 0.25 vs 0.77 +/- 0.17 ml/g/min, p <0.05), whereas MBF after vasodilatation (2.12 +/- 0.78 vs 3.10 +/- 0.85 ml/g/min, p <0.05) and coronary flow reserve (CFR) was reduced (2.5 +/- 0.88 vs 4.1 +/- 1.01, p <0.05), especially in those with impaired ventricular function. Coronary vascular resistance after vasodilatation was elevated in the FLO group (38.2 +/- 17.4 vs 24.5 +/- 8.3 mmHg/ml/g/min, p <0.05). Altered MBF, increased meridional wall stress, and impaired CFR are common findings in FLO. Attenuated CFR and reduced ventricular function are significantly correlated and may be risk factors for the long-term outcome.

Adolescent↗

Treatment of Candida albicans endocarditis: case report and a review.

Candida albicans endocarditis occurs mostly in patients with congenital heart disease; open heart surgery is the greatest predisposing factor. We report on a child with truncus arteriosus communis and a large Candida vegetation within the prosthetic pulmonary valve, causing severe right ventricular outflow tract obstruction. Treatment was performed successfully by surgery and administration of liposomal amphotericin B (AmBisome) and 5-flucytosine.

Amphotericin B↗

Radiologic diagnosis and management of complications related to central venous access.

Central venous access is an important aspect of medical treatment. There are different designs of access devices for different purposes. In essence, they can be classified as short- and long-term devices. Insertion procedures vary for different devices. There is a risk for both acute and delayed complications. Radiology plays a central role both in placement and in device management. Image-guided insertion increases technical success and reduces the rate of acute complications. The diagnostic approach to long-term complications includes radiography, fluoroscopy, CT, and ultrasound. Treatment by interventional procedures is possible for a number of these conditions. These interventions increase device lifespan and reduce the number of necessary reinsertions.

Catheterization, Central Venous↗