PubMed Health⌕ Search

Biomedical subjects

H Böttcher

Publications and source records attributed to H Böttcher.

At least 19 recordsLinked to original sources

Double-hadron leptoproduction in the nuclear medium.

The first measurements of double-hadron production in deep-inelastic scattering within the nuclear medium were made with the HERMES spectrometer at DESY HERA using a 27.6 GeV positron beam. By comparing data for deuterium, nitrogen, krypton, and xenon nuclei, the influence of the nuclear medium on the ratio of double-hadron to single-hadron yields was investigated. Nuclear effects on the additional hadron are clearly observed, but with little or no difference among nitrogen, krypton, or xenon, and with smaller magnitude than effects seen on previously measured single-hadron multiplicities. The data are compared with models based on partonic energy loss or prehadronic scattering and with a model based on a purely absorptive treatment of the final-state interactions. Thus, the double-hadron ratio provides an additional tool for studying modifications of hadronization in nuclear matter.

Journal Article↗

Development of a 3-D convolution/superposition algorithm for precise dose calculation in the skull.

In this paper an algorithm for calculating 3-D dose distributions within the brain is introduced and adapted to the demands of modem radiosurgery. The dose calculation with this model is based on a 3-D distribution of the primary photon intensity which is calculated with a ray casting algorithm. A prelocated matrix takes into account field sizes as well as modifying elements as collimator positions (MLC), blocks, wedges and compensators. Monte Carlo precalculated monoenergetic kernels from 0.1 MeV to 50 MeV were at our disposal. The components of the spectrum were either determined by deconvoluting depth dose curves measured in water or analyzed with a Ge-Li detector system in the case of 60Co. The calculated fluence distribution has to be superposed to the complete kernel containing the spatial energy deposition. Inhomogeneities and tissue interface phenomena (rhoe, Z) have been investigated. The divergence of the rays and the curved surface of the patient are taken into account. Assuming homogenous media, it is possible to shorten the computation time by using the Fast Fourier Transformation (FFT) delivering a first overview within seconds. The algorithm was evaluated and verified under specific conditions of small fields as used in radiosurgery and compared to dose measurements and Monte Carlo calculations. In using both the fast algorithm (FFT) for mainly homogenous conditions on one hand and the very precise superposition for inhomogeneous cases on the other, this algorithm can be a very helpful instrument especially for critical locations in the skull.

Algorithms↗

Measurement of the tensor structure function b1 of the deuteron.

The Hermes experiment has investigated the tensor spin structure of the deuteron using the 27.6 GeV/c positron beam of DESY HERA. The use of a tensor-polarized deuteron gas target with only a negligible residual vector polarization enabled the first measurement of the tensor asymmetry A(d)zz and the tensor structure function b(d)1 for average values of the Bjorken variable 0.01< <0.45 and of the negative of the squared four-momentum transfer 0.5 GeV2 < <5 GeV2. The quantities A(d)zz and b(d)1 are found to be nonzero. The rise of b(d)1 for decreasing values of x can be interpreted to originate from the same mechanism that leads to nuclear shadowing in unpolarized scattering.

Journal Article↗

Single-spin asymmetries in semi-inclusive deep-inelastic scattering on a transversely polarized hydrogen target.

Single-spin asymmetries for semi-inclusive electroproduction of charged pions in deep-inelastic scattering of positrons are measured for the first time with transverse target polarization. The asymmetry depends on the azimuthal angles of both the pion (phi) and the target spin axis (phi(S)) about the virtual-photon direction and relative to the lepton scattering plane. The extracted Fourier component sin((phi+phi(S))(pi)(UT) is a signal of the previously unmeasured quark transversity distribution, in conjunction with the Collins fragmentation function, also unknown. The component sin((phi-phi(S)(pi)(UT) arises from a correlation between the transverse polarization of the target nucleon and the intrinsic transverse momentum of quarks, as represented by the previously unmeasured Sivers distribution function. Evidence for both signals is observed, but the Sivers asymmetry may be affected by exclusive vector meson production.

Journal Article↗

Development of an interactive graphical user interface for therapy simulation.

Because of the ongoing development to more complex non-coplanar techniques in radiotherapy, the use of modem computer graphics while designing a dose plan becomes increasingly essential and more important. In this paper, we describe a concept to simulate 3D conformal treatment techniques on the computer. All important components of the treatment device and relevant patient structures are mapped to an internal model, which allows simulation of motion sequences as well as the interactive adjustment of treatment parameters. The intention of this user interface is to save time by using mainly graphical modules in the optimization process instead of running through the dose calculation every time.

Algorithms↗

Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX). In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n = 145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group). The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Adult↗

Flavor decomposition of the sea-quark helicity distributions in the nucleon from semiinclusive deep inelastic scattering.

Double-spin asymmetries of semiinclusive cross sections for the production of identified pions and kaons have been measured in deep inelastic scattering of polarized positrons on a polarized deuterium target. Five helicity distributions including those for three sea quark flavors were extracted from these data together with reanalyzed previous data for identified pions from a hydrogen target. These distributions are consistent with zero for all three sea flavors. A recently predicted flavor asymmetry in the polarization of the light quark sea appears to be disfavored by the data.

Journal Article↗

Evidence for quark-hadron duality in the proton spin asymmetry A1.

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry A1. Longitudinally polarized positrons were scattered off a longitudinally polarized hydrogen target for values of Q2 between 1.2 and 12 GeV2 and values of W2 between 1 and 4 GeV2. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable x. This finding implies that the description of A1 in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of Q2 above 1.6 GeV2.

Journal Article↗

Q2 dependence of nuclear transparency for exclusive rho0 production.

Exclusive coherent and incoherent electroproduction of the rho(0) meson from 1H and 14N targets has been studied at the HERMES experiment as a function of coherence length (l(c)), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon (-Q2). The ratio of 14N to 1H cross sections per nucleon, called nuclear transparency, was found to increase (decrease) with increasing l(c) for coherent (incoherent) rho(0) electroproduction. For fixed l(c), a rise of nuclear transparency with Q2 is observed for both coherent and incoherent rho(0) production, which is in agreement with theoretical calculations of color transparency.

Journal Article↗

5-HT reuptake inhibitors with 5-HT(1B/1D) antagonistic activity: a new approach toward efficient antidepressants.

As part of our research program toward new, potential antidepressants, a series of unsymmetrical ureas has been prepared and evaluated as 5-HT reuptake inhibitors with 5-HT(1B/1D) antagonistic activities. The design of these compounds was based on coupling of various indole derivatives, previously shown to inhibit 5-HT reuptake, to three different aniline moieties, which are part of known 5-HT(1B/1D) ligands. Binding experiments in rat frontal cortex using [(125)I]iodocyanopindolol, in calf striatum using [(3)H]5-HT, and in rat hippocampus using [(3)H]8-OH-DPAT as radioligands, respectively, revealed significantly higher affinity at the 5-HT(1B) receptor as compared to the affinities for the 5-HT(1A) and 5-HT(1D) receptors for a number of compounds, among them 4-(5-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide (5), the corresponding 4-fluoro-1H-indol-3-yl analogue 21a, and the corresponding 6-fluoro-1H-indol-3-yl analogue 21b. Conformational restriction of the aniline moiety in 5 only slightly enhanced the 5-HT(1B) affinity, whereas introduction of an aniline moiety with higher conformational flexibility resulted in a less potent 5-HT(1B) receptor ligand as compared to 5. The functional 5-HT(1B/1D) antagonistic activity was investigated using the rabbit saphenous vein model as well as the [(3)H]5-HT release from guinea pig cortical slices. All new compounds tested in the rabbit saphenous vein model were shown to antagonize the sumatriptan-evoked contractile responses with pA(2) values ranging from 7.3 to 8.7. These observations were consistent with the results of the cortical slice model, in which the ureas were found to block the sumatriptan-induced inhibition of potassium-evoked [(3)H]5-HT release. The 5-HT reuptake inhibition of the ureas determined in rat brain synaptosomes was found to be either increased or decreased as compared to the uncoupled indole derivatives indicating that the reuptake inhibition shown by the ureas is not only due to the indole part but also affected by the aniline moiety of the molecule. Among this series of compounds described the ureas 5, 21a, and 21b seem to be the most interesting candidates showing both 5-HT reuptake inhibition and 5-HT(1B/1D) antagonism in vitro. This dual pharmacological profile should in theory lead to a pronounced enhancement in serotonergic neurotransmission and consequently to a more efficient treatment of depression.

Animals↗

New selective and potent 5-HT(1B/1D) antagonists: chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides.

A series of new analogues of N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl] 2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-carboxamide (1; GR127935) as potent and selective 5-HT(1B/1D) antagonists were synthesized and evaluated pharmacologically. Their receptor binding profiles were comparable to that of 1. The 1,3,4-oxadiazole isomer 2 and the 4'-aminocarbonyl and 4'-amidinyl analogues (9 and 10) of 1 had higher affinities at the rat 5-HT(1B) receptor (IC(50) = 0.93, 1. 3, and 0.5 nM, respectively) and calf 5-HT(1D) receptor (IC(50) = 37, 10, and 3 nM, respectively) than did 1 (1.6 and 52 nM for rat 5-HT(1B) and calf 5-HT(1D) receptors, respectively). In the functional in vitro testing of 5-HT(1B/1D) antagonistic properties, 2, 9, 10, 11b (O-demethylated derivative of 2), 13a (O-methylsulfonyl analogue of 2), and 16 (which differs from 2 with a sulfonamide linker) showed more pronounced effects in the K(+)-induced 5-HT release in the cortex of guinea pig than did 1 and 3 (SB224289). Compounds 2, 9, and 10 were equally potent as 1 in rabbit saphenous vein model (pA(2) > 9). A biochemical study of 2 with in vivo microdialysis in the rat brain showed that it is capable of augmenting citalopram (a selective serotonin reuptake inhibitor, SSRI) induced 5-HT release in rat ventral hippocampus, while preventing the decrease in acetylcholine release elicited by citalopram administration. The molecular structure of 2 was determined by single-crystal X-ray analysis. The log P and log D values of these compounds were calculated. This study contributes to the SAR study of N-piperazinylphenyl biphenylcarboxamides as selective and potent 5-HT(1B/1D) antagonists.

Acetylcholine↗

Synthesis and in vitro and in vivo functional studies of ortho-substituted phenylpiperazine and N-substituted 4-N-(o-methoxyphenyl)aminopiperidine analogues of WAY100635.

WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values at guinea pig ileum strips) and in vivo (hypothermia and ultrasonic vocalization) pharmacology at the serotonin 5-HT(1A) receptor of several closely related analogues of 2. Test compounds 12 and 14, in which the arylpiperazine moiety of 2 has been replaced by an arylaminopiperidine moiety, showed no affinity or antagonistic activity at the 5-HT(1A) receptor. Substitution of the o-methoxy group of 2 by larger fluoroalkoxy or sulfonyloxy substituents did not alter the in vitro or in vivo pharmacology to any great extent; in vivo both the fluoropropyl analogue 5 and the triflate analogue 7 are equipotent to WAY100635 itself. The O-desmethyl analogue 3 proved to be the most potent antagonist at the serotonin 5-HT(1A) postsynaptic receptor sites in this series.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Immunoglobulin A and secretory immunoglobulin A in the bronchoalveolar lavage from patients after lung transplantation.

Secretory immunoglobulin A (sIgA) is the most important Ig on mucosal surfaces. In bronchoalveolar lavage (BAL) fluid, sIgA is mainly produced by bronchus-associated lymphoid tissue (BALT). The presence of pre-formed antibodies against donor tissue in kidney transplantation is associated with hyperacute rejection, indicating a humoral (antibody-mediated) reaction. In heart and liver transplantation, humoral rejection has also been documented. The goal of this study was to evaluate the role of IgA in patients after lung transplantation. An enzyme-linked immunosorbent assay was established to determine the levels of sIgA, IgA, and total protein in the lavage. IgA and sIgA were both detectable in BAL from transplanted lungs. IgA and sIgA levels were both higher during episodes of infection than during episodes of rejection or during the control episodes. The level of IgA during episodes of rejection equaled the level of IgA during the control episodes. The level of sIgA was significantly decreased during episodes of acute rejection (1.8 +/- 1.0 microg/mL) when compared with the control (7.2 +/- 1.0 microg/mL; p = 0.013). This study demonstrates that BALT retains the ability to produce Ig even after lung transplantation. The levels of IgA and sIgA and their ratio do not contribute to the differentiation between rejection and infection in lung-transplanted patients.

Acute Disease↗

Detection of CMV pneumonitis after lung transplantation using PCR of DNA from bronchoalveolar lavage cells.

BACKGROUND: Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. OBJECTIVE: Evaluation of methods for the rapid diagnosis of CMV pneumonitis. METHODS: The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. RESULTS: In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. CONCLUSIONS: PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis.

Adolescent↗

Sol-gel composite films with controlled release of biocides.

The release of biocides (benzoic, sorbic and boric acids) incorporated into modified silica films was investigated with respect to composite structure. The liberation rates of the embedded acids are proportional to the biocide-to-silica ratio and are changed by adding soluble polymers such as hydroxypropylcellulose. The rates of liberation correlate with biocidal activity, i.e., the growth of microorganisms such as Escherichia coli, Lactobacillus plantarum and Penicillium sp. is strongly suppressed by contact with such composite films. In a similar way, strong fungicide and insecticide effects were observed after impregnating wood with composites containing boric acid.

Benzoic Acid↗

New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation.

A series of 2- or 8-trifluoromethylsulfonyloxy (TfO) and 2- or 8-methylsulfonyloxy (MsO) 11-piperazinyldibenzodiazepines, -oxazepines, and -thiazepines were synthesized and evaluated in pharmacological models for their potential clozapine-like properties. In receptor binding assays, the 2-TfO analogues (18a, GMC2-83; 24, GMC3-06; and previously reported GMC1-169, 9a) of the dibenzazepines have profiles comparable to that of clozapine, acting on a variety of CNS receptors except they lack M1 receptor affinity. Introduction of 2-TfO to clozapine leads to compound 9e (GMC61-39) which has a similar binding profile as that of clozapine including having M1 receptor affinity. Interestingly, the MsO analogues, as well as the 8-TfO analogues, have no or weak dopaminergic and serotonergic affinities, but all 8-sulfonyloxy analogues do have M1 affinities. In behavioral studies performed to indicate the potential antipsychotic efficacy and the propensity to induce EPS, 2-TfO analogues blocked effectively the apomorphine-induced climbing in mice in a dose-dependent manner with ED50 values (mg/kg) of 2.1 sc for 9a, 1.3 po for 18a, 2.6 sc for 24, and 8.2 sc for 9e. On the other hand, they showed a clear dose separation with regard to their ED50 values (mg/kg) for indicating catalepsy in rats (>44 sc for 9a, 28 po for 18a, 30 sc for 24, and >50 sc for 9e, respectively), thus implicating a more favorable therapeutic ratio (K/A, ED50 climbing/ED50 catalepsy) in comparison with typical neuroleptics such as haloperidol and isoclozapine. Furthermore, compound 18a was also demonstrated to be an orally potent DA antagonist with an ED50 value of 0.7 mg/kg po in the ex vivo L-DOPA accumulation model. The present study contributes to the SAR of 11-piperazinyldibenzazepines, and the 2-TfO analogues of 11-piperazinyldibenzazepines are promising candidates as clozapine-like atypical antipsychotics with low propensity to induce EPS.

Animals↗

Eosinophilic alveolitis in BAL after lung transplantation.

Lung transplantation has become a therapeutic option for patients with end stage lung disease. However, outcome after transplantation is complicated by episodes of rejection and infections. Bronchoalveolar lavage is a valuable tool in monitoring patients after transplantation, since it allows the detection of pathogens. A marker specifically indicating rejection from changes in BAL fluid has not been found yet. Especially changes in differential cell count, like lymphocytosis or an increase in polymorphnuclear granulocytes, are unspecific. The role of high eosinophil levels in BAL has not been elucidated yet. We analyzed 25 BAL samples and clinical data of 4 patients who underwent lung transplantation and presented with recurrent episodes of eosinophilic alveolitis in BAL. All patients demonstrated a deterioration of clinical condition, lung function, and blood gas analysis during times of eosinophilia in BAL, compared to previous examinations. In all cases, eosinophilia in BAL was accompanied by rejection. All patients were finally treated with high doses of steroids, resulting in improvement of all parameters. Eosinophilia was not associated with significant changes in the IL-5 concentration in BAL or the pattern of IL-5 expression in BAL cells. In conclusion, eosinophilic alveolitis may indicate acute rejection in patients after lung transplantation, if other causes of eosinophilia are excluded.

Bronchoalveolar Lavage Fluid↗