Search PubMed⌕ Search

Biomedical subjects

R Brandt

Publications and source records attributed to R Brandt.

At least 19 recordsLinked to original sources

Attachment of MAL32-encoded maltase on the outside of yeast cells improves maltotriose utilization.

The fermentation of maltotriose, the second most abundant fermentable sugar in wort, is often incomplete during high-gravity brewing. Poor maltotriose consumption is due to environmental stress conditions during high-gravity fermentation and especially to a low uptake of this sugar by some industrial strains. In this study we investigated whether the use of strains with an alpha-glucosidase attached to the outside of the cell might be a possible way to reduce residual maltotriose. To this end, the N-terminal leader sequence of Kre1 and the carboxy-terminal anchoring domain of either Cwp2 or Flo1 were used to target maltase encoded by MAL32 to the cell surface. We showed that Mal32 displayed on the cell surface of Saccharomyces cerevisiae laboratory strains was capable of hydrolysis of alpha-1,4-linkages, and that it increased the ability of a strain lacking a functional maltose permease to grow on maltotriose. Moreover, the enzyme was also expressed and found to be active in an industrial strain. These data show that expressing a suitable maltase on the cell surface might provide a means of modifying yeast for more complete maltotriose utilization in brewing and other fermentation applications.

Beer↗

Prognostic value of N-terminal pro-B-type natriuretic peptide for conservatively and surgically treated patients with aortic valve stenosis.

OBJECTIVE: To evaluate the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with aortic stenosis being treated conservatively or undergoing aortic valve replacement (AVR). METHODS: 159 patients were followed up for a median of 902 days. 102 patients underwent AVR and 57 were treated conservatively. NT-proBNP at baseline was raised in association with the degree of severity and of functional status. RESULTS: During follow up 21 patients (13%) died of cardiac causes or required rehospitalisation for decompensated heart failure. NT-proBNP at baseline was higher in patients with an adverse outcome than in event-free survivors (median 623 (interquartile range 204-1854) pg/ml v 1054 (687-2960) pg/ml, p = 0.028). This difference was even more obvious in conservatively treated patients (331 (129-881) pg/ml v 1102 (796-2960) pg/ml, p = 0.002). Baseline NT-proBNP independently predicted an adverse outcome in the entire study group and in particular in conservatively treated patients (area under the curve (AUC) = 0.65, p = 0.028 and AUC = 0.82, p = 0.002, respectively) but not in patients undergoing AVR (AUC = 0.544). At a cut-off value of 640 pg/ml, baseline NT-proBNP was discriminative for an adverse outcome. CONCLUSION: NT-proBNP concentration is related to severity of aortic stenosis and provides independent prognostic information for an adverse outcome. However, this predictive value is limited to conservatively treated patients. Thus, the data suggest that assessing NT-proBNP may have incremental value for selecting the optimal timing of valve replacement.

Aged↗

Detection of spallation neutrons and protons using the (nat)Cd activation technique in transmutation experiments at Dubna.

Various spallation sources have been used to transmute long-lived radioactive waste, mostly making use of the wide energy neutron fluence. In addition to neutrons, a large number of protons and gamma rays are also emitted from these sources. In this paper (nat)Cd is proved to be a useful activation detector for determining both thermal-epithermal neutron as well as secondary proton fluences. The fluences measured with (nat)Cd compared with other experimental data and calculations of DCM-DEM code were found to be in reasonable agreement. An accumulation of thermal-epithermal neutrons around the center of the target (i.e. after approx. 10 cm) and of secondary protons towards the end of the target is observed.

Journal Article↗

Nickel release, a possible indicator for the duration of antiplatelet treatment, from a nickel cardiac device in vivo: a study in patients with atrial septal defects implanted with an Amplatzer occluder.

UNLABELLED: The present study was undertaken to evaluate the safety and release of nickel after implantation of a nickel device (Amplatzer occluder) in patients with an atrial septal defect (ASD) receiving antiplatelet therapy. METHODS: Blood and urine samples were obtained from 24 patients with ASD before occluder implantation (baseline) and during a 12-month post closure period. Antiplatelet drugs were administered for the initial 6-month period post implantation. The nickel content in the specimens was determined using electrothermal atomic absorption spectroscopy. The clinical, sonographic and magnetic resonance imaging follow-ups were carried out 1 week, 1 month, 6 months and 12 months post implantation. RESULTS: Mean baseline concentrations of nickel in serum and urine were within normal range with values of 0.6 +/- 0.2 microg/l and 3.1 +/- 1.2 microg/l, respectively. During the 6-week post closure period, the time needed for the formation of neointima on the surface of the graft, nickel levels in serum increased up to 5-fold (p < 0.01 versus baseline). Mean concentrations in serum and urine returned to baseline levels within 4-6 months post implantation. All patients showed satisfactory clinical improvements and there was no sonographic evidence of complications. CONCLUSIONS: The initial dissolution of nickel from the Amplatzer occluder is not a specific cardiovascular risk and is temporarily linked to the formation of the non-thrombogenic neointima on the surface of the graft. The antiplatelet drug regimen used (300 mg aspirin + 75 mg clopidogrel daily for 3 months in the initial phase and 100 mg aspirin daily for a further 3 months) appears to cover the period of neointima formation on the nickel device when nickel levels are significantly elevated. However, further studies in a larger number of patients and over a period greater than 12 months are needed to confirm the validity of these conclusions and to formulate definitive recommendations on the duration of the antiplatelet treatment.

Adult↗

Transcatheter closure of a ruptured ventricular septum after myocardial infarction using a venous approach.

A 65-year old patient was admitted after having sustained a ventricular septum rupture 18 days after an anterior myocardial infarction. He developed acute heart failure. Given the extremely high perioperative risk in surgical approaches in this setting, we decided for a transcatheter closure of the defect with an exclusively venous approach. After a complete recovery, the patient underwent open heart surgery with aorto coronary bypass, aneurysmectomy, and removal of the closure device. This case demonstrates that transcatheter closure of a post infarction ventricular septum rupture is a technically feasible and suitable method.

Aged↗

Arsenic contamination in water, soil, sediment and rice of central India.

Arsenic contamination in the environment (i.e. surface, well and tube-well water, soil, sediment and rice samples) of central India (i.e. Ambagarh Chauki, Chhattisgarh) is reported. The concentration of the total arsenic in the samples i.e. water (n = 64), soil (n = 30), sediment (n = 27) and rice grain (n = 10) were ranged from 15 to 825 microg L(-1), 9 to 390 mg kg(-1), 19 to 489 mg kg(-1) and 0.018 to 0.446 mg kg(-1), respectively. In all type of waters, the arsenic levels exceeded the permissible limit, 10 microg L(-1). The most toxic and mobile inorganic species i.e. As(III) and As(V) are predominantly present in water of this region. The soils have relatively higher contents of arsenic and other elements i.e. Mg, Al, Si, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Ga, Zr, Sn, Sb, Pb and U. The mean arsenic contents in soil of this region are much higher than in arsenic soil of West Bengal and Bangladesh. The lowest level of arsenic in the soil of this region is 3.7 mg kg(-1) with median value of 9.5 mg kg(-1). The arsenic contents in the sediments are at least 2-folds higher than in the soil. The sources of arsenic contamination in the soil of this region are expected from the rock weathering as well as the atmospheric deposition. The environmental samples i.e. water, soil dust, food, etc. are expected the major exposure for the arsenic contamination. The most of people living in this region are suffering with arsenic borne diseases (i.e. melanosis, keratosis, skin cancer, etc.).

Arsenic↗

[Cardiopulmonary exercise capacity increases after interventional ASD-closure].

BACKGROUND: In patients with atrial septal defects of the secundum-type (ASD), exercise tolerance is reduced. Generally, ASD closure is recommended in symptomatic patients and in patients with a relevant left-to-right shunt (Qp/Qs > 1.5). Only few data are available concerning objective parameters of cardiopulmonary exercise capacity. The aim of this study was to evaluate exercise capacity as achieved by ergospirometry in adult patients with an ASD at baseline and in the long-term following transcatheter closure. METHODS AND RESULTS: Thirty consecutive patients (8 male; mean age 43.4 years; defect size 23.5 mm; pulmonary-to-systemic flow ratio (Qp/Qs) 1.94) performed exercise testing on a supine bicycle ergometer. At baseline, oxygen consumption at maximal exercise (VO(2) peak) was 14.3 ml/min kg, oxygen consumption at the anaerobic threshold (VO(2)-AT) was 11.2 ml/min/kg and maximal achieved workload was 86 Watt. At one and six months after ASD-closure, there was no relevant increase of the VO(2) peak, the VO(2)-AT or the maximal workload. After 12 months, there was a significant increase of the VO(2) peak (15.1 ml/min/kg, p = 0.049), the VO(2)-AT (13 ml/min/kg, p < 0.001) and the maximal workload (99 Watt, p < 0.01). An increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT) could be seen in 24 out of 30 patients and was independent of shunt volume (Q(p)/Q(s) < or = 2, 1.95 ml/ min/kg; Q(p)/Q(s) > 2, 2.13 ml/min/ kg; ns), defect size (defect < or = 24 mm, 2.0 ml/min/kg; defect > 24 mm, 1.5 ml/min/kg; ns), age (age < or = 44 years, 1.97 ml/min/kg; age >44 years, 1.66 ml/min/kg; ns), gender (female 1.56 ml/min/ kg; male 1.91 ml/min/kg; ns) and of the existence of a residual shunt. Highly symptomatic patients had a tendency to have greater benefit from ASD-closure as compared to mildly symptomatic patients (NYHA 0/I 1.85 ml/min/kg; NYHA II 1.5 ml/min/ kg; NYHA III 2.7 ml/min/kg; ns). There was no correlation between shunt volume, shunt size, pulmonal arterial pressure and increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT). CONCLUSION: There is no relevant improvement in exercise capacity early (1-6 months) after interventional ASD-closure, but late after ASD-closure (12 months) exercise capacity improves significantly. This improvement can be found in almost all patients independent of gender, age, symptoms, shunt volume and defect size.

Adolescent↗

The automatic pilot of honeybees.

Using scanning harmonic radar, we make visible for the first time the complete trajectories of "goal-vector" flights in honeybees. We demonstrate that bees captured at an established feeding station, and released elsewhere, nevertheless embark on the previously learned vector flight that would have taken them directly home from the station, had they not been artificially displaced. Almost all of the bees maintained accurate compensation for lateral wind drift, and many completed the full length of the vector flight before starting to search for their hive. Our results showed that bees tend to disregard landscape cues during these vector flights, at least initially, and rely on the "optic flow" of the ground beneath them, and their sun compass, to judge both direction and distance.

Animals↗

Application of activation methods on the Dubna experimental transmutation set-ups.

High spallation neutron fluxes were produced by irradiating massive heavy targets with proton beams in the GeV range. The experiments were performed at the Dubna High Energy Laboratory using the nuclotron accelerator. Two different experimental set-ups were used to produce neutron spectra convenient for transmutation of radioactive waste by (n,x) reactions. By a theoretical analysis neutron spectra can be reproduced from activation measurements. Thermal-epithermal and fast-super-fast neutron fluxes were estimated using the 197Au, 238U (n,gamma) and (n,2n) reactions, respectively. Depleted uranium transmutation rates were also studied in both experiments.

Journal Article↗

Differential parallel processing of olfactory information in the honeybee, Apis mellifera L.

Two distinct neuronal pathways connect the first olfactory neuropil, the antennal lobe, with higher integration areas, such as the mushroom bodies, via antennal lobe projection neurons. Intracellular recordings were used to address the question whether neuroanatomical features affect odor-coding properties. We found that neurons in the median antennocerebral tract code odors by latency differences or specific inhibitory phases in combination with excitatory phases, have a more specific activity profile for different odors and convey the information with a delay. The neurons of the lateral antennocerebral tract code odors by spike rate differences, have a broader activity profile for different odors, and convey the information quickly. Thus, rather preliminary information about the olfactory stimulus first reaches the mushroom bodies and the lateral horn via neurons of the lateral antennocerebral tract and subsequently odor information becomes more specified by activities of neurons of the median antennocerebral tract. We conclude that this neuroanatomical feature is not related to the distinction between different odors, but rather reflects a dual coding of the same odor stimuli by two different neuronal strategies focusing different properties of the same stimulus.

Action Potentials↗

Functions and malfunctions of the tau proteins.

The tau proteins belong to the family of microtubule-associated proteins. They are mainly expressed in neurons where they play major regulatory roles in the organization and integrity of the cytoskeleton network. Neurofibrillary changes of abnormally hyperphosphorylated tau are a key lesion in Alzheimer's disease and a number of other tauopathies. However, despite an ever-increasing body of data on the changes which tau undergoes in disease, its role regarding the fundamental disease process is still unclear. Moreover, conceptions of tau functions continue to evolve, which complicates an understanding of its role in the disease process. This review attempts to summarize data on the role of tau proteins in the context of both normal cellular function and dysfunction. Furthermore, we try to develop a mechanistic framework for the involvement of tau during the disease process. The review closes with a look towards various approaches to elucidate the functions and malfunctions of tau.

Alzheimer Disease↗

Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a novel orthotopic tumor model for testing anti-cancer agents.

The ErbB2 receptor tyrosine kinase (RTK) has been intensely pursued as a cancer therapy target due to its association with breast cancer. In this study we used the HC11 mammary epithelial cell line to develop an orthotopic, ErbB2-driven tumor model for testing efficacy of anti-cancer compounds. HC11 cells were infected with a retrovirus encoding oncogenic NeuT, the rat homolog of ErbB2. Drug-selected populations were introduced into mammary fat pads of Balb/c syngeneic mice cleared of host tissue. The majority of glands injected with HC11-NeuT cells developed mammary tumors which appeared after a 3-4 week latency period and grew rapidly. HC11 cells infected with the control retrovirus showed no tumor growth after injection. Tumor-bearing mice were used to compare the in vivo efficacy of two anti-cancer agents: PKI166, a kinase inhibitor selective for EGF receptor and ErbB2, and Taxol, a microtubule assembly blocker. PKI166 inhibited NeuT-induced mammary tumor growth in a dose-dependent manner and at a dose below the maximum tolerated dose (MTD) was significantly more inhibitory than Taxol at its MTD (57% vs. 25% tumor regression). Importantly, there was a dose-dependent decrease in the phosphotyrosine content of NeuT isolated from PKI166-treated, tumor-bearing mice, providing a mechanistic link between kinase inhibition and its anti-tumor activity. Thus, implantation of genetically manipulated HC11 cells into mammary glands appears to be an excellent model for studying effects of anti-cancer agents in an orthotopic site.

Animals↗

Phosphorylation-mimicking glutamate clusters in the proline-rich region are sufficient to simulate the functional deficiencies of hyperphosphorylated tau protein.

The microtubule-associated tau proteins represent a family of closely related phosphoproteins that become enriched in the axons during brain development. In Alzheimer's disease (AD), tau aggregates somatodendritically in paired helical filaments in a hyperphosphorylated form. Most of the sites that are phosphorylated to a high extent in paired helical filament tau are clustered in the proline-rich region (P-region; residues 172--251) and the C-terminal tail region (C-region; residues 368--441) that flank tau's microtubule-binding repeats. This might point to a role of a region-specific phosphorylation cluster for the pathogenesis of AD. To determine the functional consequences of such modifications, mutated tau proteins were produced in which a P- or C-region-specific phosphorylation cluster was simulated by replacement of serine/threonine residues with glutamate. We show that a phosphorylation-mimicking glutamate cluster in the P-region is sufficient to block microtubule assembly and to inhibit tau's interaction with the dominant brain phosphatase protein phosphatase 2A isoform AB alpha C. P-region-specific mutations also decrease tau aggregation into filaments and decrease tau's process-inducing activity in a cellular transfection model. In contrast, a phosphorylation-mimicking glutamate cluster in the C-region is neutral with regard to these activities. A glutamate cluster in both the P- and C-regions induces the formation of SDS-resistant conformational domains in tau and suppresses tau's interaction with the neural membrane cortex. The results indicate that modifications in the proline-rich region are sufficient to induce the functional deficiencies of tau that have been observed in AD. They suggest that phosphorylation of the proline-rich region has a crucial role in mediating tau-related changes during disease.

Binding Sites↗

Development of a procedure for the multi-element determination of trace elements in wine by ICP-MS.

An inductively coupled plasma mass spectrometric (ICP-MS) procedure has been developed for the determination of trace elements in wine. The procedure consists in simple 1+1 dilution of the wine and semi-quantitative analysis (without external calibration) using In as internal standard. Thirty-one elements at concentrations ranging from 0.1 mg mL(-1) to 0.5 ng mL(-1) can be determined by ICP-MS analysis with and without digestion. It was investigated whether a matrix effect observed for EtOH in the wine matrix can be overcome by application of a micro-concentric nebulizer with a membrane desolvator (MCN 6000). The results obtained for the MCN 6000 are compared with those obtained by use of a conventional Meinhard nebulizer. It is shown that the observed matrix effect can only be compensated by use of an internal standard for the Meinhard nebulizer, but not for the MCN 6000. Results for ICP-MS are compared with those obtained by total reflection X-ray fluorescence spectrometry (TXRF).

Ethanol↗

Cytoskeletal mechanisms of neuronal degeneration.

The cytoskeleton is the major intracellular determinant of neuronal morphology and is required for fundamental processes during the development and maintenance of a neuron. Thus, it is not surprising that many neurodegenerative diseases including Alzheimer's disease and amyotrophic lateral sclerosis (motor neuron disease) are characterized by typical abnormalities in the organization of the cytoskeleton. However, the role of the cytoskeletal changes during the development of the disease, e.g., whether they have a causative role during neuronal degeneration or represent an epiphenomenon of neurons that degenerate by other means, is still disputed. In this review, recent results on the development and the role of cytoskeletal abnormalities during neurodegenerative diseases are discussed and a mechanistic framework for the involvement of cytoskeletal changes during neurodegenerative processes is presented.

Alzheimer Disease↗

Colour thresholds and receptor noise: behaviour and physiology compared.

Photoreceptor noise sets an absolute limit for the accuracy of colour discrimination. We compared colour thresholds in the honeybee (Apis mellifera) with this limit. Bees were trained to discriminate an achromatic stimulus from monochromatic lights of various wavelengths as a function of their intensity. Signal-to-noise ratios were measured by intracellular recordings in the three spectral types of photoreceptor cells. To model thresholds we assumed that discrimination was mediated by opponent mechanisms whose performance was limited by receptor noise. Most of the behavioural thresholds were close to those predicted from receptor signal-to-noise ratios, suggesting that colour discrimination in honeybees is affected by photoreceptor noise. Some of the thresholds were lower than this theoretical limit, which indicates summation of photoreceptor cell signals.

Animals↗