[Clinical significance of leptin].
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Adipose Tissue↗
Biomedical subjects
W Becker
Publications and source records attributed to W Becker.
Above-threshold ionization by an elliptically polarized field: interplay between electronic quantum trajectories
Measurements of energy-resolved angular distributions of electrons generated in above-threshold ionization of rare gases in a field with elliptical polarization are presented, with emphasis on the high-energy part of the spectra. The data show a second plateau at a specific angle with respect to the large component of the laser field. The results are compared to a calculation based on a strong-field rescattering approximation. This is interpreted in terms of the superposition of quantum trajectories. The second plateau is associated with the interference of electrons that do and that do not rescatter.
Journal Article↗
Rescattering processes for elliptical polarization: A quantum trajectory analysis
High-harmonic generation and high-order above-threshold ionization spectra calculated in the strong-field approximation are analyzed in terms of the complex space-time orbits that result from a saddle point analysis of the underlying integrals. For elliptical polarization, the plateaus of the spectra of high-harmonic generation and high-order above-threshold ionization each turn into a staircase of very similar appearance. Each step of the stair can be traced to a particular pair of orbits which are almost identical in both cases.
Journal Article↗
Collective multielectron tunneling ionization in strong fields
We investigate the quantum mechanical process of two-electron tunneling in strong external electric fields. Numerical solution of a two-electron s-wave model reveals the existence of collective tunneling ionization in a mode where both electrons stay at equal distance from the nucleus. Otherwise the lagging electron is immediately recaptured. The corresponding double ionization rate fails to explain nonsequential multiple ionization in strong-field laser experiments. However, an empirically modified version of the analytical one-electron tunneling rate of Ammosov, Delone, and Krainov agrees with the experiments to a surprising accuracy. The reason for this agreement is presently unknown.
Journal Article↗
Bird Keeper's lung without bird keepinge
The identification of disease inducing allergens in hypersensitivity pneumonitis can be very problematic, and only by a thorough analysis of anamnestic data the source of allergen can be identified. We report a case of a 32-year-old female diagnosed with hypersensitivity pneumonitis caused by the inhalation of budgerigar antigen in her home. She had been living there for two years and had never been a bird keeper at all. The former proprietor of the house was a budgerigar keeper for years. When we detected precipitating antibodies against different antigens including pigeon and budgerigar antigens as well as hay and Aureobasidium pullulans, the source of antigen exposition was not definitely clear. In the serum of our patient we found precipitating antibodies against protein structures extracted from dust samples from the patient's home, which were not detected in the serum of her husband. Using Western blots of budgerigar serum and of the dust sample from the patient's home we could demonstrate an IgG reactive banding pattern in our patient's serum. The banding pattern against budgerigar serum correlated very closely to that of a control patient, who was a budgerigar keeper with hypersensitivity pneumonitis. The patient's husband reacted neither against budgerigar serum nor against the dust sample, while he and his wife showed double banding at about 9 kDA, when their serum was exposed to dust from a home free of bird keeping. These results point to the fact, that the house dust sample of our patient contained budgerigar antigen, leading to an indirect antigen expositon causing hypersensitivity alveolitis. However, the positive reaction of the patient serum against the protein extract from the dust sample of her home needs further confirmation by inhibition experiments using budgerigar antigen. - Our patient received a prolonged treatment with corticosteroids, and after about one year the vital capacity of the lungs, which was reduced by 50% at the beginning of the treatment, returned to normal. The patient is still living in her home. Although she has been off medication for one year, lung function has not deteriorated. This fact points to a reduction of the amount of antigen in the patient's home.
Journal Article↗
Specificity determinants of substrate recognition by the protein kinase DYRK1A.
DYRK1A is a dual-specificity protein kinase that is thought to be involved in brain development. We identified a single phosphorylated amino acid residue in the DYRK substrate histone H3 (threonine 45) by mass spectrometry, phosphoamino acid analysis, and protein sequencing. Exchange of threonine 45 for alanine abolished phosphorylation of histone H3 by DYRK1A and by the related kinases DYRK1B, DYRK2, and DYRK3 but not by CLK3. In order to define the consensus sequence for the substrate specificity of DYRK1A, a library of 300 peptides was designed in variation of the H3 phosphorylation site. Evaluation of the phosphate incorporation into these peptides identified DYRK1A as a proline-directed kinase with a phosphorylation consensus sequence (RPX(S/T)P) similar to that of ERK2 (PX(S/T)P). A peptide designed after the optimal substrate sequence (DYRKtide) was efficiently phosphorylated by DYRK1A (K(m) = 35 microM) but not by ERK2. Both ERK2 and DYRK1A phosphorylated myelin basic protein, whereas only ERK2, but not DYRK1A, phosphorylated the mitogen-activated protein kinase substrate ELK-1. This marked difference in substrate specificity between DYRK1A and ERK2 can be explained by the requirement for an arginine at the P -3 site of DYRK substrates and its presumed interaction with aspartate 247 conserved in all DYRKs.
Amino Acid Sequence↗
123I-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis.
OBJECTIVE: To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10), 123I-labeled, serine proteinase inhibitor antileukoproteinase (123I-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). METHODS: Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 microg of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). 123I-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6). The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography. Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. RESULTS: ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with AIA. In both knee joints, 123I-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. CONCLUSION: Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA. These findings underscore the high sensitivity of 123I-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA.
Animals↗
Highlights of the annual meeting of the European Association of Nuclear Medicine, Barcelona 1999. Scientific-based functional imaging and therapy for the next millennium.
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Animals↗
[Improved detection of gastrointestinal bleeding sites with 99mTc market autologous erythrocytes and continuous dynamic scintigraphy with cine-mode display].
BACKGROUND: Scintigraphic studies of gastrointestinal bleeding are usually performed in static acquisition mode and without continuous imaging over a longer period. The aim of this study was to evaluate the diagnostic accuracy of continuous dynamic 99mTc red blood cell scintigraphy (BQS) and cine-mode display in the assessment of unexplained gastrointestinal bleeding. PATIENTS AND METHODS: We performed BQS in 40 patients (mean age 57 years) with gastrointestinal bleeding from an undetermined source. All these patients had negative findings of previous examinations. Blood transfusions were required in 16 patients. Continuous dynamic scintigraphic acquisition was performed up to 6 h post injection (p.i.). The scintigraphic data were reviewed without knowledge of the patient's final diagnosis. For this purpose we used a cine-mode display. RESULTS: Dynamic 99mTc red blood cell scintigraphy correctly identified the site of active bleeding in 22 of 23 patients with positive scintigraphic findings. The sensitivity of the scan was 95%, the specificity 94%, the positive and negative predictive values 95% and 94%, respectively. Forty-three percent of the scans became positive within 1.5 h and 82% within 5 h. Positive scans were more likely in patients who required blood transfusions than in patients without transfusion requirement (16 vs 7 patients), and the bleeding site was identified earlier in the former group (mean 2.83 vs 5.28 h p.i.). The scintigraphic identification of the bleeding lesions enabled the performance of a more limited surgical approach in the colon as well as in the distal small intestine, while exact scintigraphic localization was not possible if the bleeding site was located in the proximal small intestine. DISCUSSION: Continuous dynamic 99mTc red blood cell scintigraphy interpreted by cine-mode display is highly accurate in the identification of a bleeding site. When performed correctly, scintigraphy enables usually segmental resection of these lesions.
Diagnosis, Differential↗
[The diagnostic potentials of nuclear medicine in chronic infections].
BACKGROUND: The availability of high-sensitive radiopharmaceuticals for the diagnosis of an unknown focus of infection with whole body scanning and SPECT and the availability of high specific radiopharmaceuticals for the detection of a leucocytic infiltration are the basis of the high potential of nuclear medicine in patients with chronic infections. Both procedures are always complementary to radiological procedures, which can specify and better determine a detected focus and which can induce also infection imaging if the radiologic result is ambiguous. RADIOPHARMACEUTICALS: Not all available radiopharmaceuticals for the nuclear medicine imaging of infection and inflammation, i.e. 99mTc-nanocolloids, 99mTc-labelled human immunoglobulin, 99mTc-HMPAO and 111In-oxin labelled leukocytes, 67Ga-citrate, 99mTc-labelled antigranulocyte antibodies and their fragments and 18F-FGD-PET, are useful in all clinical situations, because there are differences in the availability, the radiation exposure, the costs and the underlying patho-physiological mechanism.
Chronic Disease↗
[Nuclear medicine study potentials in diseases of the skeletal system].
Even though new diagnostic methods, as CT/MRI, are widely available, the bone scintigraphy still does remain an important tool for imaging bone pathology. An increase in diagnostic accuracy is possible by using different imaging modalities: wholebody scan, three phase bone scintigraphy and SPECT. For this reason, the bone scintigraphy can be used for diagnosis of tumors/infections and therapy monitoring. Applying these methods, important informations can be gained for differential diagnosis. The bone scintigraphy is easy to perform, allows good whole-body overview by low radiation burden to the patient.
Bone Diseases↗
[Radiosynoviorthesis in inflammatory joint diseases].
The use of beta-(beta) emitting radionuclides for radiosynoviorthesis (RSO) has been a well established therapy for inflammed joints for more than 40 years. Radionuclides are often applied to patients with rheumatoid arthritis as local therapy. The choice of the radionuclide is empirical. The evaluation of the therapeutic success is mainly based on the improvement of the joint motion. MRI and other radiological examinations have not been proved to be reliable for diagnosis of the therapeutic success. The aims of this manuscript are to familiarize physicians with the different radionuclides, to explain the therapeutic success which can be expected due to dosimetric data, and to present the three phase bone scintigraphy as a valuable instrument for the evaluation of the therapeutic success.
Arthritis, Rheumatoid↗
Vestibular perception of self-rotation in different postures: a comparison between sitting and standing subjects.
We investigated whether posture - either seated (S) or upright standing (O, orthostatic) - affects the vestibular perceptions of angular velocity (V) and displacement (D) in the horizontal plane. We also examined whether the two perceptions are equivalent, that is, whether perceived displacement can be viewed as the time integral of perceived velocity. Sinusoidal stimuli were delivered to subjects sitting on a Barany chair or standing on a turning platform. Frequencies ranged from 0.028 Hz to 0.45 Hz, peak-to-peak amplitudes from 11.3 degrees to 180 degrees, and peak velocities from 4 degrees/s to 64 degrees/s. Perceptions were measured by retrospective magnitude estimation in relation to a standard stimulus (STD) of 0.11 Hz, 45 degrees, 16 degrees/s. For D-estimates, two different moduli were assigned to the STD: Either "45 degrees" (allowing subjects to use the familiar degree scale, which can easily be related to the body scheme) or "10" (which bears no relation to an accustomed scale). For V-estimations the modulus was always "10" (there is no "natural" velocity scale). D-estimates exhibited only a marginal, non-significant dependence on posture (S larger than O); they were highly veridical (linear function of stimulus amplitude, gain close to 1) when subjects used the degree scale but had a reduced gain (approximately 0.76) with a modulus of 10. V-estimates, on the other hand, varied with posture (S significantly larger than O), particularly upon presentation of large stimuli; also, they deviated increasingly from veracity as stimulus magnitude increased (saturating function). Finally, posture had no effect upon the vestibular detection threshold. The frequency response of D-estimates, tested with stimuli of constant amplitude and varying frequency, was bimodal at low frequencies: stimuli were either not detected at all or were veridically estimated, on average (with a large scatter, though). The frequency response of V-estimates, tested with stimuli of constant peak velocity, exhibited a continuous increase with stimulation frequency. We conclude that published quantifications of vestibular self-motion perception, collected mostly with sitting subjects, are likely to be applicable also to the more natural situation of standing subjects provided they are based on displacement indications; in contrast, velocity indications appear to be modulated by posture. The different susceptibility of displacement and velocity estimates to posture and their incongruent frequency characteristics suggest that perceived displacement does not, or does not always, equal the time integral of perceived velocity. The persistence of nearly veridical displacement estimates at low frequencies suggests the intervention of cognitive processes.
Acceleration↗
Therapeutic advantages of Auger electron- over beta-emitting radiometals or radioiodine when conjugated to internalizing antibodies.
Recent studies suggest a higher anti-tumour efficacy of internalizing monoclonal antibodies (MAbs) when labelled with Auger electron emitters, as compared with beta-emitters. The aim of this study was to compare the anti-tumour efficacy and toxicity of the internalizing MAb, CO17-1A, labelled with Auger electron emitters (125I, (111)In) versus conventional beta(-)-emitters (131I, 90Y) in a colon cancer model, and to assess whether the residualizing radiometals may have therapeutic advantages over the conventionally iodinated conjugates. Biodistribution studies of 125I-, (111)In- or 88Y-labelled CO17-1A were performed in nude mice bearing subcutaneous human colon cancer xenografts. For therapy, the mice were injected with either unlabelled or 125I-, 131I-, (111)In- or 90Y-labelled CO17-1A IgG2a, whereas control groups were left untreated or were given a radiolabelled isotype-matched irrelevant antibody. The influence of internalization was assessed by comparing the results with those obtained with an anti-carcinoembryonic antigen (CEA) antibody which does not internalize to a relevant extent. The maximum tolerated activities (MTA) and doses (MTD) of each agent were determined. Myelotoxicity and potential second-organ toxicities, as well as tumour growth, were monitored. Bone marrow transplantation (BMT) was performed in order to enable dose intensification. Radiometals showed significantly better tumour-to-blood ratios than the respective iodinated conjugates. The MTAs of 131I- and 125I-CO17-1A without artificial support were 11.1 MBq (300 microCi) and 111 MBq (3 mCi), respectively; the MTA of the metals was reached at 4 MBq (100 microCi) for 90Y-, and at 85 MBq (2.3 mCi) for (111)In-CO17-1A. Myelotoxicity was dose limiting in all cases. BMT enabled an increase in the MTA to 15 MBq (400 microCi) of 131I-labelled CO17-1A, to 4.4 MBq (120 microCi) of 90Y-labelled CO17-1A, and to 118 MBq (3.2 mCi) of (111)In-labelled CO17-1A, while the MTA of 125I-CO17-1A had not been reached at 185 MBq (5 mCi) with BMT. Whereas no significant therapeutic effects were seen with unlabelled CO17-1A, tumour growth was retarded significantly with its radiolabelled forms. The therapeutic results were significantly (P<0.01) better with both Auger electron emitters (125I and (111)In) than with the beta-emitters, and, in accordance with the biodistribution data, a trend towards better therapeutic results was found with radiometals (more complete remissions) as compared with radioiodine. In contrast, at equitoxic doses, no significant difference was observed in the therapeutic efficacy of 131I- versus 125I-labelled non-internalizing anti-CEA antibody, F023C5. These data suggest that, at equitoxic doses, the therapeutic efficacy of internalizing MAbs labelled with Auger electron emitters, such as 125I or (111)In, is superior to that of internalizing MAbs labelled with conventional beta-emitters. The lower toxicity of Auger electron emitters may be due to the short path length of their low-energy electrons, which can reach the nuclear DNA only if the antibody is internalized (as is the case in antigen-expressing tumour tissue, but not in the stem cells of the red marrow).
Animals↗
Radioiodine therapy for Plummer's disease based on the thyroid uptake of technetium-99m pertechnetate.
The aim of this retrospective study was the evaluation of a TcTUs (global technetium-99m pertechnetate thyroid uptake under suppression)-based approach in 370 patients with thyroid autonomy (Plummer's disease) treated by radioiodine therapy (RIT) under standardised conditions. The analysis included 370 patients (309 females, 61 males; mean age 64+/-11.6 years) treated for thyroid autonomy [unifocal (UFA), 36.8%; multifocal (MFA), 55.7%; disseminated (DISA), 7.6%]. During RIT all patients were under thyroid suppression (TSH< 0.1 microU/ml) and without thionamide treatment. Of the 370 patients, 73% (n=271) were manifestly hyperthyroid and 27% (n=99) subclinically hyperthyroid. A dosimetric study included uptake measurements 24, 48, and 96 h p.i. For dose estimation the Marinelli algorithm was used. For retrospective definition of the target volume we used the equation: Autonomous volume = TcTUs x 5. The spectrum of doses given in our patients ranged from 81 to 1933 Gy. After 18 months of follow-up, RIT was successful (TSH>0.5 microqU/l and/or TcTUs<1.6%) in 310 patients (84%). Of these patients, 291 (94%) were euthyroid (with or without L-thyroxine) and 19 (6%) subclinically hypothyroid (TSH>4 microU/ml). A dose of 350-450 Gy to the autonomous tissue resulted in a success rate of 97% in the UFA group and 81% in the MFA/DISA group. Decrease in total thyroid volume and TcTUs did not differ significantly between successfully treated patients and patients with persistent autonomy. Multivariate analysis of all 370 patients identified four independent factors that negatively influenced the therapeutic success: high pretherapeutic thyroid volume (P=0.0001; odds ratio: 1.017), high pretherapeutic TcTUs values (P=0.0001; odds ratio: 1.378), multifocal/disseminated autonomy (P=0.0056; odds ratio: 3.245) and low target dose (P=0.017; odds ratio: 0.997). It is concluded that the high success rate in the treatment of UFA indicates the concept of TcTUs-based RIT to be valid, but that in the therapy of MFA/DISA the target dose has to be corrected if the total thyroid volume exceeds a critical threshold.
Adult↗
Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET.
Gallium-67 citrate is currently considered as the tracer of first choice in the diagnostic workup of fever of unknown origin (FUO). Fluorine-18 2'-deoxy-2-fluoro-D-glucose (FDG) has been shown to accumulate in malignant tumours but also in inflammatory processes. The aim of this study was to prospectively evaluate FDG imaging with a double-head coincidence camera (DHCC) in patients with FUO in comparison with planar and single-photon emission tomography (SPET) 67Ga citrate scanning. Twenty FUO patients underwent FDG imaging with a DHCC which included transaxial and longitudinal whole-body tomography. In 18 of these subjects, 67Ga citrate whole-body and SPET imaging was performed. The 67Ga citrate and FDG images were interpreted by two investigators, both blinded to the results of other diagnostic modalities. Forty percent (8/20) of the patients had infection, 25% (5/20) had auto-immune diseases, 10% (2/20) had neoplasms and 15% (3/20) had other diseases. Fever remained unexplained in 10% (2/20) of the patients. Of the 20 patients studied, FDG imaging was positive and essentially contributed to the final diagnosis in 11 (55%). The sensitivity of transaxial FDG tomography in detecting the focus of fever was 84% and the specificity, 86%. Positive and negative predictive values were 92% and 75%, respectively. If the analysis was restricted to the 18 patients who were investigated both with 67Ga citrate and FDG, sensitivity was 81% and specificity, 86%. Positive and negative predictive values were 90% and 75%, respectively. The diagnostic accuracy of whole-body FDG tomography (again restricted to the aforementioned 18 patients) was lower (sensitivity, 36%; specificity, 86%; positive and negative predictive values, 80% and 46%, respectively). 67Ga citrate SPET yielded a sensitivity of 67% in detecting the focus of fever and a specificity of 78%. Positive and negative predictive values were 75% and 70%, respectively. A low sensitivity (45%), but combined with a high specificity (100%), was found in planar 67Ga imaging. Positive and negative predictive values were 100% and 54%, respectively. It is concluded that in the context of FUO, transaxial FDG tomography performed with a DHCC is superior to 67Ga citrate SPET. This seems to be the consequence of superior tracer kinetics of FDG compared with those of 67Ga citrate and of a better spatial resolution of a DHCC system compared with SPET imaging. In patients with FUO, FDG imaging with either dedicated PET or DHCC should be considered the procedure of choice.
Adult↗
The human sodium-iodine symporter (NIS) as a key for specific thymic iodine-131 uptake.
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Carrier Proteins↗
Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group.
OBJECTIVE: This randomized, double-blind, crossover study was undertaken to compare the incidence of headache recurrence after treatment with naratriptan or sumatriptan in migraine patients with a history of frequent headache recurrence (recurrence in > or =50% of successfully treated attacks). BACKGROUND: Although the selective 5-hydroxytryptamine, (5-HT1) agonist sumatriptan is effective and well tolerated for acute treatment of migraine in most patients, headache recurrence within 24 hours of initial successful treatment with sumatriptan and other medications has been reported in approximately 35% of patients. The novel 5-HT1 agonist naratriptan possesses pharmacologic and pharmacokinetic characteristics that may address the issue of headache recurrence. METHODS: Men and women aged 18 to 65 years with a > or =1-year history of migraine with or without aura were randomly assigned to treat 1 moderate or severe migraine attack in a nonclinical setting with one 2.5-mg naratriptan tablet and 1 attack with one 100-mg sumatriptan tablet. A pain-free interval of > or =24 hours was required between attacks. At 4 hours, patients not using rescue medication and experiencing headache recurrence could take a second, identical dose of study medication to treat recurrence. No more than 2 tablets of study medication were permitted in any 24-hour period. RESULTS: A total of 253 patients treated > or =1 migrane attack and were included in the safety analysis; the 225 patients who treated both attacks were included in the efficacy analysis. Of the 164 naratriptan-treated and 181 sumatriptan-treated patients experiencing headache relief after > or =1 attack, headache recurrence 4 to 24 hours after treatment was reported by 74 naratriptan-treated patients (45%) and 101 sumatriptan-treated patients (57%; not statistically significant). (One naratriptan- and 3 sumatriptan-treated patients who experienced headache relief did not record recurrence status and were not included in the denominator for the percentage calculation.) In a subset of patients experiencing headache relief after 2 attacks, headache recurrence 4 to 24 hours after initial dosing was reported by 55 naratriptan- and 77 sumatriptan-treated patients (41% and 57%, respectively; P = 0.005). The overall incidence of adverse events was 22% after treatment with naratriptan and 33% after treatment with sumatriptan. This incidence did not increase after use of a second dose of naratriptan (20%) or sumatriptan (31%). CONCLUSION: These data suggest that naratriptan is a long-acting and well-tolerated addition to currently available medications for the treatment of acute migraine.
Adolescent↗