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Biomedical subjects

W Becker

Publications and source records attributed to W Becker.

At least 19 recordsLinked to original sources

Immediate implant placement: treatment planning and surgical steps for successful outcomes.

Diagnosis and treatment planning are key factors in achieving successful outcomes after placing and restoring implants placed immediately after tooth extraction. The efficacy of immediate implant placement has been established and shown to be predictable if reasonable guidelines are followed. Some or all of the following suggestions, depending on individual circumstances, should be considered when evaluating a patient for dental implants: thorough medical and dental histories, clinical photographs, study casts, periapical and panogram radiographs as well as a linear tomography or computerised tomography of the proposed implant sites. Reasons for tooth extraction include but are not limited to: insufficient crown to root ratios, remaining root length, periodontal attachment levels, periodontal health of teeth adjacent to the proposed implant sites, unrestorable caries, root fractures with large endodontic posts, root resorption, teeth with deep furcation invasions being considered as abutments for fixed partial dentures and questionable teeth in need of endodontic retreatment.

Animals↗

High-order harmonic generation in a tightly focused laser beam.

The force due to the transverse magnetic field of a laser beam drives an electron in the direction of laser propagation, thereby impeding the recollision mechanism for high-order harmonic generation. The longitudinal electric field component of a tightly focused Gaussian beam can sufficiently counteract the magnetic force to enhance the harmonic yield substantially. For tight focusing and a laser intensity of 10(18) W/cm2, it can raise the harmonic yield by several orders of magnitude.

Journal Article↗

Dietary intake estimations of organohalogen contaminants (dioxins, PCB, PBDE and chlorinated pesticides, e.g. DDT) based on Swedish market basket data.

By use of a Swedish Market basket study from 1999, in which foods were sampled from four regions, the dietary intake of persistent organic pollutants (POPs) was assessed. Based on earlier data, six food groups (fish, meat, dairy products, egg, fats/oils, and pastries; comprising 52 food items) were selected for POP analyses. Homogenates from these six groups were subjected to POP analyses and levels presented on dioxins (PCDD/PCDFs), dioxin-like PCBs, PCB-153, summation operatorPCBs, BDE-47, summation operatorPBDEs, DDE, summation operatorDDTs, HCB, summation operatorHCHs, and summation operatorchlordanes, after adjusting non-quantified levels to 1/2 LOQ. For all compounds, the fish homogenate contained the comparatively highest levels, on a fresh weight basis. Intake calculations based on the six food groups showed that summation operatorPCBs and summation operatorDDTs gave per capita intakes of 615 and 523 ng/day, respectively, that the estimated summation operatorPBDE intake was 51 ng/day and that of dioxins and dioxin-like PCBs was 96 pg WHO-TEQ/day. The estimated mean intakes were below (total-TEQ: 1.3 pg/kgbw/day) or well below (summation operatorDDTs: 8.9 ng/kgbw/day) internationally agreed intake limits (total-TEQ: 2 pg/kgbw/day; summation operatorDDTs: 10,000 ng/kgbw/day). A number of uncertainty factors, including analytical limitations due to low POP levels in food, give reason for caution in the use of the presented intake data. However, the intake estimations of dioxins, summation operatorPCBs and summation operatorPBDEs are well in accordance to calculations of POP intakes in Sweden made by alternate methods.

Diet↗

Fluorescence lifetime images and correlation spectra obtained by multidimensional time-correlated single photon counting.

Multidimensional time-correlated single photon counting (TCSPC) is based on the excitation of the sample by a high-repetition rate laser and the detection of single photons of the fluorescence signal in several detection channels. Each photon is characterized by its arrival time in the laser period, its detection channel number, and several additional variables such as the coordinates of an image area, or the time from the start of the experiment. Combined with a confocal or two-photon laser scanning microscope and a pulsed laser, multidimensional TCSPC makes a fluorescence lifetime technique with multiwavelength capability, near-ideal counting efficiency, and the capability to resolve multiexponential decay functions. We show that the same technique and the same hardware can be used for precision fluorescence decay analysis and fluorescence correlation spectroscopy (FCS) in selected spots of a sample.

Cell Line↗

Smooth pursuit rather than visual signals mediate short-term adaptation of the cervico-ocular reflex in humans.

Cervical stimulation in the horizontal plane induces small and variable eye movements in normal human adults [cervico-ocular reflex (COR)]. In patients with bilateral vestibular loss, the slow COR component increases in amplitude and is thought to contribute to gaze stabilization during head movements, as it is directed opposite to head-on-trunk excursions. The procedures underlying COR slow phase gain enhancement in the compensatory direction remain unclear. We studied the horizontal COR during passive trunk oscillations of +/-16 degrees under the stationary head at 0.1 Hz in ten normal subjects, aged 24-30 years, before and immediately after the application of an adaptation procedure engaging various combinations of sinusoidal neck-proprioceptive, pursuit and retinal slip signals. The duration of this adaptation period was 40 min. A significant gain increase and phase modulation in the compensatory direction were observed in four out of eight subjects after exposing them to neck-proprioceptive stimulation, while pursuing a spot moving in-phase with their trunk. In contrast, staring at the rotating optokinetic pattern or fixating at a stationary spot, while being subjected to combined cervical and optokinetic stimulation, failed to result in any significant modification of the subjects' COR gain and phase. Conceivably, the contribution of the pursuit system was greatly reduced in the paradigm using optokinetic stimulation, while full engagement of retinal slip signals, in the absence of any pursuit contribution, was obtained in the latter adaptation paradigm. These results indicate that motor responses of target tracking rather than simply sensory signals of retinal slip may represent the 'error signal' modifying the COR in humans.

Adaptation, Physiological↗

Attosecond double-slit experiment.

A new scheme for a double-slit experiment in the time domain is presented. Phase-stabilized few-cycle laser pulses open one to two windows (slits) of attosecond duration for photoionization. Fringes in the angle-resolved energy spectrum of varying visibility depending on the degree of which-way information are measured. A situation in which one and the same electron encounters a single and a double slit at the same time is observed. The investigation of the fringes makes possible interferometry on the attosecond time scale. From the number of visible fringes, for example, one derives that the slits are extended over about 500 as.

Journal Article↗

Parameter investigation for decentralised dewatering and solar thermic drying of sludge.

The purpose of this paper is an experimental and model assisted investigation of the capabilities of a dewatering system for sewage sludge for decentralised sites. Laboratory and field tests are performed with different initial conditions and the influences of filter medium, initial height, initial total suspended solids, temperature and relative humidity are discussed. The experimental work shows the feasibility of geotextile media for dewatering high water content sewage sludge and that the textile structure is of secondary importance. The specific filter resistance of the sludge cake is found to be the most significant factor in dewatering applications. The mathematical description of the dewatering process is based on the superposition of two models, the Conventional Filtration Theory for the filtration phase and the BT-model for the drying phase. Feasibility and limits of the theoretical approach are evaluated by means of a comparison between measurements and simulated data of cyclic reloading tests. It is found that a better filtration efficiency is achieved at higher TSS and at lower initial height of the slurry layer. Due to the viscosity decrease, a higher temperature enhances not only evaporation, but also filtration rate.

Filtration↗

Fluorescence lifetime imaging by time-correlated single-photon counting.

We present a time-correlated single photon counting (TCPSC) technique that allows time-resolved multi-wavelength imaging in conjunction with a laser scanning microscope and a pulsed excitation source. The technique is based on a four-dimensional histogramming process that records the photon density over the time of the fluorescence decay, the x-y coordinates of the scanning area, and the wavelength. The histogramming process avoids any time gating or wavelength scanning and, therefore, yields a near-perfect counting efficiency. The time resolution is limited only by the transit time spread of the detector. The technique can be used with almost any confocal or two-photon laser scanning microscope and works at any scanning rate. We demonstrate the application to samples stained with several dyes and to CFP-YFP FRET.

Animals↗

Erythropoietin: a candidate compound for neuroprotection in schizophrenia.

Erythropoietin (EPO) is a candidate compound for neuroprotection in human brain disease capable of combating a spectrum of pathophysiological processes operational during the progression of schizophrenic psychosis. The purpose of the present study was to prepare the ground for its application in a first neuroprotective add-on strategy in schizophrenia, aiming at improvement of cognitive brain function as well as prevention/slowing of degenerative processes. Using rodent studies, primary hippocampal neurons in culture, immunohistochemical analysis of human post-mortem brain tissue and nuclear imaging technology in man, we demonstrate that: (1) peripherally applied recombinant human (rh) EPO penetrates into the brain efficiently both in rat and humans, (2) rhEPO is enriched intracranially in healthy men and more distinctly in schizophrenic patients, (3) EPO receptors are densely expressed in hippocampus and cortex of schizophrenic subjects but distinctly less in controls, (4) rhEPO attenuates the haloperidol-induced neuronal death in vitro, and (4) peripherally administered rhEPO enhances cognitive functioning in mice in the context of an aversion task involving cortical and subcortical pathways presumably affected in schizophrenia. These observations, together with the known safety of rhEPO, render it an interesting compound for neuroprotective add-on strategies in schizophrenia and other human diseases characterized by a progressive decline in cognitive performance.

Adult↗

Multimodal imaging in the elastase-induced aneurysm model in rabbits: a comparative study using serial DSA, MRA and CTA.

BACKGROUND AND PURPOSE: The elastase-induced aneurysm model in rabbits has proved to be suitable for testing new endovascular occlusion devices. The purpose of this study was to evaluate different imaging modalities for the depiction of anatomy and size of elastase-induced aneurysms and for serial follow-up imaging. MATERIALS AND METHODS: Elastase-induced aneurysms were created in eight Chinchilla bastard rabbits by endoluminal incubation of porcine elastase. Serial imaging was performed using intravenous DSA (IVDSA), contrast-enhanced MRA (CEMRA), and time-of-flight MRA (TOF) 14 days, 4 weeks and 3 months after aneurysm creation. Intraarterial DSA (IADSA) and CT angiography (CTA) were performed after 3 months. Aneurysm size and geometry (height H, width W, neck width N) were compared. RESULTS: On IVDSA after two weeks mean aneurysm height was 6.2 mm (range 2.8 - 11.0 mm), mean aneurysm width was 2.8 mm (range 2.0 - 4.2 mm) and mean aneurysm neck width was 2.7 mm (range 2.0 - 4.2 mm). We did not observed any statistically significant change in aneurysm dimensions during follow-up at 4 weeks (CEMRA: H: 5.4, W: 2.4, N: 2.4; TOF: H: 5.7, W: 2.4, N: 2.7) and 3 months (CEMRA: H: 5.8, W: 2.6, N: 2.6; TOF: H: 6.9, W: 2.8, N: 3.0). Aneurysm dimensions could be best seen on IADSA (H: 6.2, W: 3.0, N: 2.7) with good correlation to CTA (r = 0.94; H: 6.1, W: 2.8, N: 2.6), CE-MRA (r = 0.92), and TOF (r = 0.97). TOF was superior to CEMRA in delineating the aneurysm wall. CONCLUSIONS: Serial imaging using MRA, CTA or intravenous and intraarterial angiography is feasible in the elastase-induced aneurysm model. Contrast-enhanced MRA, TOF-MRA and CTA showed good correlation to IADSA and are all suitable for non-invasive pretherapeutic measurement of aneurysm size.

Angiography↗

[Gastrostromy tube feeding of elderly inpatients in Bremen].

Tube feeding has become a common procedure among patients of nursing homes. Reliable data about prevalence in nursing homes, medical and nutritional indications are not available on local or national level. The Public Health Office in Bremen conducted a questionnaire based survey of all nursing homes in August 2003 in which 56 of 62 institutions participated (90.3 %) and 4,300 of 4,549 patients (94 %) could be included. Prevalence of patients with gastrostomy tubes (PEG) varied between 0 and 16.7 % and was higher than expected with an average of 7.8 %. The evaluation of reported medical indications, patients' problems and decision-making showed need of further vocational training and guidelines which include ethical aspects. The results of the survey were presented to and discussed with the staffs of nursing homes at a conference in February 2004.

Aged↗

Differential hepatic gene expression in a polygenic mouse model with insulin resistance and hyperglycemia: evidence for a combined transcriptional dysregulation of gluconeogenesis and fatty acid synthesis.

New Zealand obese (NZO) mice exhibit severe insulin resistance of hepatic glucose metabolism. In order to define its biochemical basis, we studied the differential expression of genes involved in hepatic glucose and lipid metabolism by microarray analysis. NZOxF1 (SJLxNZO) backcross mice were generated in order to obtain populations with heterogeneous metabolism but comparable genetic background. In these backcross mice, groups of controls (normoglycemic/normoinsulinemic), insulin-resistant (normoglycemic/hyperinsulinemic) and diabetic (hyperglycemic/hypoinsulinemic) mice were identified. At 22 weeks, mRNA was isolated from liver, converted to cDNA, and used for screening of two types of cDNA arrays (high-density filter arrays and Affymetrix oligonucleotide microarrays). Differential gene expression was ascertained and assessed by Northern blotting. The data indicate that hyperinsulinemia in the NZO mouse is associated with: (i) increased mRNA levels of enzymes involved in lipid synthesis (fatty acid synthase, malic enzyme, stearoyl-CoA desaturase) or fatty acid oxidation (cytochrome P450 4A14, ketoacyl-CoA thiolase, acyl-CoA oxidase), (ii) induction of the key glycolytic enzyme pyruvate kinase, and (iii) increased mRNA levels of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects were enhanced by a high-fat diet. In conclusion, the pattern of gene expression in insulin-resistant NZO mice appears to reflect a dissociation of the effects of insulin on genes involved in glucose and lipid metabolism. The data are consistent with a hypothetical scenario in which an insulin-resistant hepatic glucose production produces hyperinsulinemia, and an enhanced insulin- and substrate-driven lipogenesis further aggravates the deleterious insulin resistance of glucose metabolism.

Animals↗

An in vitro study to compare 99mTc-stannous colloids and 99mTc-HMPAO for labelling human leukocytes.

AIM: Aim of the present study was to compare in vitro the labelling efficiency (LE) and cell viability (TBE) of autologous leukocytes labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO, and to evaluate the quantity and quality of spontaneously released (99m)Tc (SR) from labelled cells at several time points after labelling. METHODS: A total of 14 patients with different diseases and 18 normal subjects were included in this study. A blood sample was collected from each patient; purified autologous leukocytes were divided into 2 samples and labelled with (99m)Tc-SnF(2) and (99m)Tc-HMPAO. LE was evaluated at the end of labelling and TBE and SR were evaluated at 10 min and 1 h, 2 h and 4 h after labelling. RESULTS: LE of (99m)Tc-SnF(2)-WBC was higher than (99m)Tc-HMPAO-WBC (61.2+/-18.7% and 43.3+/-11.3; p<0.0001) and we found an inverse correlation between blood glucose and labelling efficiency for both methods (p=0.02). Minimal differences were also observed between 2 methods after 10 min and 1 h, as far as the cell viability is concerned. The percentage of radioactivity spontaneously released from (99m)Tc-SnF(2)-WBC was significantly higher compared to (99m)Tc-HMPAO-WBC at each time point. Radioactivity released from labelled cells was predominantly (99m)Tc-SnF(2) and (99m)Tc-HMPAO with few free (99m)Tc (<20%). CONCLUSION: Both radiopharmaceuticals are not toxic for WBC. Labelling with (99m)Tc-SnF(2) give a higher LE than with (99m)Tc-HMPAO; however, radiolabelled colloids are more released from labelled cells over a period of 4 h. While (99m)Tc-HMPAO is physiological excreted into gastrointestinal tract, (99m)Tc-SnF(2) can be re-uptaken in vivo by reticulo-endothelial cells of liver and spleen. These findings suggest that (99m)Tc-SnF(2)-WBC might be better than (99m)Tc-HMPAO-WBC for studying inflammatory bowel diseases.

Cells, Cultured↗

Phase I clinical trial of the bispecific antibody MDX-H210 (anti-FcgammaRI x anti-HER-2/neu) in combination with Filgrastim (G-CSF) for treatment of advanced breast cancer.

A phase I study of the bispecific antibody MDX-H210 in combination with granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody (mAb) H22 to Fc gamma receptor I (FcgammaRI), and mAb 520C9 to HER-2/neu, respectively, mediates the lysis of tumour cells in vitro, and in human FcgammaRI transgenic mouse models. The proto-oncogene HER-2/neu is overexpressed in approximately 30% of breast cancer patients, and represents a promising target for antibody-based immunotherapy. Fc gamma receptor I (CD64) is an effective trigger molecule, which is expressed on monocytes/macrophages, immature dendritic cells, and G-CSF-primed polymorphonuclear cells (PMN). Patients received G-CSF (Filgrastim) for 8 consecutive days, and cohorts of three patients were treated on day 4 with escalating, single doses of MDX-H210. A total of 30 patients were included, and treatment was generally well tolerated, without reaching dose-limiting toxicity. Side effects consisted mainly of fever and short periods of chills, which were timely related to elevated plasma levels of interleukin 6 and tumour necrosis factor alpha. In the last two cohorts, MDX-H210 plasma levels exceeded 1 microg ml(-1), and on circulating myeloid cells >50% saturation of FcgammaRI was found until day 4. These effector cells were highly effective in antibody-dependent cell-mediated cytotoxicity. Immunohistochemical analyses of tumour biopsies in individual patients documented infiltration of monocytes and PMN after MDX-H210 infusion. Although the clinical course of the disease was not altered by the single dose of MDX-H210, a favourable toxicity profile--even at high doses--and remarkable biological effects were seen when combined with G-CSF. Therefore, the combination of G-CSF and MDX-H210 should be evaluated in further immunotherapeutical strategies.

Adjuvants, Immunologic↗

STAT3 is enriched in nuclear bodies.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is involved in a variety of biological functions. It is essential for the signal transduction of interleukin-6 (IL-6) and related cytokines. In response to IL-6 stimulation STAT3 becomes phosphorylated and translocates into the nucleus where it binds to enhancer sequences of target genes. We found that activated STAT3 is enriched in dot-like structures within the nucleus, which we termed STAT3 nuclear bodies. To examine the dynamics of STAT3 nuclear body formation, a fusion protein of STAT3 and yellow fluorescent protein (YFP) was constructed. Studies in living cells have shown that the appearance of STAT3 nuclear bodies is transient, correlating with the timecourse of tyrosine-phosphorylation of STAT3. Furthermore, we show by fluorescence recovery after photobleaching (FRAP) analysis that STAT3 within nuclear bodies consists of a highly mobile and an immobile fraction. Colocalization studies provided evidence that these bodies are accompanied with CREB binding protein (CBP) and acetylated histone H4, which are markers for transcriptionally active chromatin. Moreover, STAT3 nuclear bodies in HepG2 cells are not colocalized with promyelocytic leukemia oncoprotein (PML)-containing bodies; neither is a sumoylation of activated STAT3 detectable. Taken together, our data suggest that STAT3 nuclear bodies are either directly involved in active gene transcription or they serve as reservoirs of activated STAT3.

Animals↗

Geminga's tails: a pulsar bow shock probing the interstellar medium.

We report the X-ray Multimirror Mission-Newton European Photon Imaging Camera observation of two elongated parallel x-ray tails trailing the pulsar Geminga. They are aligned with the object's supersonic motion, extend for approximately 2', and have a nonthermal spectrum produced by electron-synchrotron emission in the bow shock between the pulsar wind and the surrounding medium. Electron lifetime against synchrotron cooling matches the source transit time over the x-ray features' length. Such an x-ray detection of a pulsar bow shock (with no Halpha emission) allows us to gauge the pulsar electron injection energy and the shock magnetic field while constraining the angle of Geminga's motion and the local matter density.

Journal Article↗

The MNB/DYRK1A protein kinase: neurobiological functions and Down syndrome implications.

Major attention is being paid in recent years to the genes harbored within the so called Down syndrome Critical Region of human chromosome 21. Among them, those genes with a possible brain function are becoming the focus of intense research due to the numerous neurobiological alterations and cognitive deficits that Down syndrome individuals have. MNB/DYRK1A is one of these genes. It encodes a protein kinase with unique genetic and biochemical properties, which have been evolutionarily conserved from insects to humans. MNB/DYRK1A is expressed in the developing brain where it seems to play a role in proliferation of neural progenitor cells, neurogenesis, and neuronal differentiation. Although at a lower level, MNB/DYRK1A is also expressed in the adult brain where, as judged by the phenotype of mutant and transgenic animals, it may be involved in learning and memory. Nevertheless, most of the molecular mechanisms underlying these functions remain to be unraveled. In this review we compile and discuss experimental evidences, which support the involvement of MNB/DYRK1A in several neuropathologies and cognitive deficits of Down syndrome.

Animals↗

The MNB/DYRK1A protein kinase: genetic and biochemical properties.

The "Down syndrome critical region" of human chromosome 21 has been defined based on the analysis of rare cases of partial trisomy 21. Evidence is accumulating that DYRK1A, one of the 20 genes located in this region, is an important candidate gene involved in the neurobiological alterations of Down syndrome. Both the structure of the DYRK1A gene and the sequence of the encoded protein kinase are highly conserved in evolution. The protein contains a unique assembly of structural motifs outside the catalytic domain, including a nuclear localization signal, a PEST region, and a repeat of 13 consecutive histidines. MNB/DYRK1A and related kinases are unique among serine/threonine-specific protein kinases in that their activity depends on tyrosine autophosphorylation in the catalytic domain. Also, evidence is accumulating that mRNA levels of MNB/DYRK1A are subject to tight regulation. A number of putative substrates of MNB/DYRK1A have emerged in the recent years, the majority of them being transcription factors. Although the function of MNB/DYRK1A in intracellular signalling and regulation of cell function is still poorly defined, current evidence suggests that the kinase may play a role in the regulation of gene expression.

Amino Acid Sequence↗