Showing papers by "University of Jena published in 2003"
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19 May 2003TL;DR: A survey of the known solutions of Einstein's field equations for vacuum, Einstein-Maxwell, pure radiation and perfect fluid sources can be found in this paper, where the solutions are ordered by their symmetry group, their algebraic structure (Petrov type) or other invariant properties such as special subspaces or tensor fields and embedding properties.
Abstract: A paperback edition of a classic text, this book gives a unique survey of the known solutions of Einstein's field equations for vacuum, Einstein-Maxwell, pure radiation and perfect fluid sources. It introduces the foundations of differential geometry and Riemannian geometry and the methods used to characterize, find or construct solutions. The solutions are then considered, ordered by their symmetry group, their algebraic structure (Petrov type) or other invariant properties such as special subspaces or tensor fields and embedding properties. Includes all the developments in the field since the first edition and contains six completely new chapters, covering topics including generation methods and their application, colliding waves, classification of metrics by invariants and treatments of homothetic motions. This book is an important resource for graduates and researchers in relativity, theoretical physics, astrophysics and mathematics. It can also be used as an introductory text on some mathematical aspects of general relativity.
3,502 citations
TL;DR: Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS, and a homology model for SARS coronavirus (SARS-CoV) Mpro is constructed.
Abstract: A novel coronavirus has been identified as the causative agent of severe acute respiratory syndrome (SARS). The viral main proteinase (Mpro, also called 3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. We determined crystal structures for human coronavirus (strain 229E) Mpro and for an inhibitor complex of porcine coronavirus [transmissible gastroenteritis virus (TGEV)] Mpro, and we constructed a homology model for SARS coronavirus (SARS-CoV) Mpro. The structures reveal a remarkable degree of conservation of the substrate-binding sites, which is further supported by recombinant SARS-CoV Mpro-mediated cleavage of a TGEV Mpro substrate. Molecular modeling suggests that available rhinovirus 3Cpro inhibitors may be modified to make them useful for treating SARS.
1,503 citations
TL;DR: Light propagating in linear and nonlinear waveguide lattices exhibits behaviour characteristic of that encountered in discrete systems, which can be exploited to achieve diffraction-free propagation and minimize the power requirements for nonlinear processes.
Abstract: Light propagating in linear and nonlinear waveguide lattices exhibits behaviour characteristic of that encountered in discrete systems. The diffraction properties of these systems can be engineered, which opens up new possibilities for controlling the flow of light that would have been otherwise impossible in the bulk: these effects can be exploited to achieve diffraction-free propagation and minimize the power requirements for nonlinear processes. In two-dimensional networks of waveguides, self-localized states--or discrete solitons--can travel along 'wire-like' paths and can be routed to any destination port. Such possibilities may be useful for photonic switching architectures.
1,426 citations
TL;DR: Evidence is found that the association of caregiver burden with the number of care Giving tasks, perceived uplifts of caregiving, and the level of physical impairment of the care receiver were stronger in probability samples than in convenience samples.
Abstract: In the present meta-analysis, we integrated findings from 228 studies on the association of six caregiving-related stressors and caregiving uplifts with burden and depressed mood. Care recipients' behavior problems showed stronger associations with caregiver outcomes than other stressors did. The size of the relationships varied by sample characteristics: Amount of care provided and care receivers' physical impairments were less strongly related to burden and depression for dementia caregivers than for caregivers of nondemented older adults. For spouse caregivers, physical impairments and care recipients' behavior problems had a stronger relationship to burden than for adult children. Furthermore, we found evidence that the association of caregiver burden with the number of caregiving tasks, perceived uplifts of caregiving, and the level of physical impairment of the care receiver were stronger in probability samples than in convenience samples.
980 citations
University of Colorado Denver1, University of Jena2, Brown University3, University of Calgary4, Complutense University of Madrid5, St Thomas' Hospital6, Université catholique de Louvain7, University of Manitoba8, Ghent University9, Memorial Hospital of South Bend10, University of Helsinki11, Autonomous University of Barcelona12, Novartis13, Pfizer14
TL;DR: Treatment with tifacogin had no effect on all-cause mortality in patients with severe sepsis and high INR and tifACogin administration was associated with an increase in risk of bleeding, irrespective of baseline INR.
Abstract: Context The expression and release of tissue factor is a major trigger for the activation of coagulation in patients with sepsis. Tissue factor pathway inhibitor (TFPI) forms a complex with tissue factor and blood protease factors leading to inhibition of thrombin generation and fibrin formation. Objectives To determine if administration of tifacogin (recombinant TFPI) provides mortality benefit in patients with severe sepsis and elevated international normalized ratio (INR) and to assess tifacogin safety in severe sepsis, including patients with low INR. Design and Setting A randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted from March 21, 2000, through September 27, 2001, in 245 hospitals in 17 countries in North America, Europe, and Israel. Patients The primary efficacy population consisted of 1754 patients (≥18 years) with severe sepsis and a high INR (≥1.2) randomly assigned to intravenous infusion of either tifacogin (0.025 mg/kg per hour for 96 hours, n = 880) or placebo (arginine citrate buffer, n = 874), and 201 patients with a low INR ( Main Outcome Measure All-cause 28-day mortality. Results Overall mortality at 28 days in the tifacogin-treated group (n = 880) vs the placebo group (n = 874) for high INR was 34.2% vs 33.9%, respectively ( P = .88, Pearson χ 2 test; P = .75, logistic regression model). None of the protocol-specified secondary end points differed between the tifacogin vs placebo groups. An analysis on the first 722 patients demonstrated a mortality rate of 38.9% for placebo vs 29.1% for tifacogin ( P = .006, Pearson χ 2 test). Tifacogin significantly attenuated prothrombin fragment 1.2 and thrombin:antithrombin complex levels ( P t test) in patients with high and low INR. Overall mortality was lower in the tifacogin response in patients with low INR (12%; n = 83) vs placebo (22.9%; n = 118) ( P =.051, Pearson χ 2 test; P = .03, logistic regression model). There was an increase in serious adverse events with bleeding in the tifacogin group in both cohorts (6.5% tifacogin and 4.8% placebo for high INR; 6.0% tifacogin and 3.3% placebo for low INR). Conclusions Treatment with tifacogin had no effect on all-cause mortality in patients with severe sepsis and high INR. Tifacogin administration was associated with an increase in risk of bleeding, irrespective of baseline INR.
916 citations
TL;DR: The deep branching of the MADS-box gene tree is described to place the MIKC(c)-type genes into an evolutionary context and reveal that the diversity of MADs-box genes in Arabidopsis is rather ancient and representative for other flowering plants.
812 citations
TL;DR: The novel noninvasive multiphoton autofluorescence-SHG imaging technique provides 4-D (x,y,z,tau) optical biopsies with subcellular resolution and offers the possibility of introducing a high-resolution optical diagnostic method in dermatology.
Abstract: High-resolution four-dimensional (4-D) optical tomography of human skin based on multiphoton autofluorescence imaging and second harmonic generation (SHG) was performed with the compact femtosecond laser imaging system DermaInspect as well as a modified multiphoton microscope. Femtosecond laser pulses of 80 MHz in the spectral range of 750 to 850 nm, fast galvoscan mirrors, and a time-correlated single-photon counting module have been used to image human skin in vitro and in vivo with subcellular spatial and 250-ps temporal resolution. The nonlinear induced autofluorescence originates from naturally endogenous fluorophores and protein structures such as reduced nicotinamide adenine dinucleotide phosphate, flavins, collagen, elastin, porphyrins, and melanin. Second harmonic generation was used to detect collagen structures. Tissues of patients with dermatological disorders such as psoriasis, fungal infections, nevi, and melanomas have been investigated. Individual intratissue cells and skin structures could be clearly visualized. Intracellular components and connective tissue structures could be further characterized by fluorescence excitation spectra, by determination of the fluorescence decay per pixel, and by fluorescence lifetime imaging. The novel noninvasive multiphoton autofluorescence-SHG imaging technique provides 4-D (x,y,z,tau) optical biopsies with subcellular resolution and offers the possibility of introducing a high-resolution optical diagnostic method in dermatology.
606 citations
TL;DR: In this article, the mean gas and dust opacities relevant to the physical conditions typical of protoplanetary discs were calculated for temperatures between 5 K and 10 000 K and gas densities ranging from 10 −18 gc m −3 to 10 −7 gcm −3.
Abstract: In this paper, we present mean gas and dust opacities relevant to the physical conditions typical of protoplanetary discs. As the principal absorber for temperatures below ∼1500 K, we consider spherical and aggregate dust particles of various sizes, chemical structure, and porosity, consisting of ice, organics, troilite, silicates, and iron. For higher temperatures, ions, atoms, molecules, and electrons are included as the main opacity sources. Rosseland and Planck mean opacities are calculated for temperatures between 5 K and 10 000 K and gas densities ranging from 10 −18 gc m −3 to 10 −7 gc m −3 . The dependence on the adopted model of dust grains is investigated. We compare our results with recent opacity tables and show how different opacity models affect the calculated hydrodynamical structure of accretion discs.
604 citations
TL;DR: In this paper, the first true three-dimensional integrated optical device, a 1×3 splitter fabricated in pure fused silica, is presented, and the optical properties of this device and possibilities for the fabrication of complex high-density integrated optical elements are discussed.
Abstract: Using tightly focussed femtosecond laser pulses, waveguides can be fabricated inside various glasses and crystals. This technique has the potential to generate not only planar but three-dimensional photonic devices. In this paper we present, to the best of our knowledge, the first true three-dimensional integrated optical device, a 1×3 splitter fabricated in pure fused silica. The optical properties of this device and possibilities for the fabrication of complex high-density integrated optical elements are discussed.
575 citations
TL;DR: It is proposed that activation of RAGE contributes to expression of VEGF and enhanced attraction/activation of inflammatory cells in the diabetic glomerulus, thereby setting the stage for mesangial activation and TGF-beta production; processes which converge to cause albuminuria and glomerulosclerosis.
Abstract: Diabetic nephropathy ensues from events involving earliest changes in the glomeruli and podocytes, followed by accumulation of extracellular matrix in the mesangium. Postulated mechanisms include roles for vascular endothelial growth factor (VEGF), produced by podocytes and contributing to enhanced excretion of urinary albumin and recruitment/activation of inflammatory cells, and transforming growth factor-β (TGF-β), elicited largely from mesangial cells and driving production of extracellular matrix. RAGE, a receptor for advanced glycation endproducts (AGEs) and S100/calgranulins, displays enhanced expression in podocytes of genetically diabetic db/db mice by age 13 weeks. RAGE-bearing podocytes express high levels of VEGF by this time, in parallel with enhanced recruitment of mononuclear phagocytes to the glomeruli; events prevented by blockade of RAGE. By age 27 weeks, soluble RAGE-treated db/db mice displayed diminished albuminuria and glomerulosclerosis, and improved renal function. Diabetic homozygous RAGE null mice failed to develop significantly increased mesangial matrix expansion or thickening of the glomerular basement membrane. We propose that activation of RAGE contributes to expression of VEGF and enhanced attraction/activation of inflammatory cells in the diabetic glomerulus, thereby setting the stage for mesangial activation and TGF-β production; processes which converge to cause albuminuria and glomerulosclerosis.
575 citations
TL;DR: Time-resolved X-ray diffraction measurements of the coherent atomic displacement of the lattice atoms in photoexcited bismuth close to a phase transition are reported, which leads to a subsequent loss of long-range order.
Abstract: The study of phase-transition dynamics in solids beyond a time-averaged kinetic description requires direct measurement of the changes in the atomic configuration along the physical pathways leading to the new phase. The timescale of interest is in the range 10(-14) to 10(-12) s. Until recently, only optical techniques were capable of providing adequate time resolution, albeit with indirect sensitivity to structural arrangement. Ultrafast laser-induced changes of long-range order have recently been directly established for some materials using time-resolved X-ray diffraction. However, the measurement of the atomic displacements within the unit cell, as well as their relationship with the stability limit of a structural phase, has to date remained obscure. Here we report time-resolved X-ray diffraction measurements of the coherent atomic displacement of the lattice atoms in photoexcited bismuth close to a phase transition. Excitation of large-amplitude coherent optical phonons gives rise to a periodic modulation of the X-ray diffraction efficiency. Stronger excitation corresponding to atomic displacements exceeding 10 per cent of the nearest-neighbour distance-near the Lindemann limit-leads to a subsequent loss of long-range order, which is most probably due to melting of the material.
TL;DR: This work has shown that the redox state of photosynthetic electron transport components and redox-active soluble molecules act as regulating parameters for photosynthesis, and provides a feedback response loop in which the expression of photosynthesis genes is coupled to the function of the photosynthesis process.
TL;DR: The data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development, and raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
Abstract: Oxidation products of low-density lipoproteins have been suggested to promote inflammation during atherogenesis, and reticulocyte-type 15-lipoxygenase has been implicated to mediate this oxidation. In addition, the 5-lipoxygenase cascade leads to formation of leukotrienes, which exhibit strong proinflammatory activities in cardiovascular tissues. Here, we studied both lipoxygenase pathways in human atherosclerosis. The 5-lipoxygenase pathway was abundantly expressed in arterial walls of patients afflicted with various lesion stages of atherosclerosis of the aorta and of coronary and carotid arteries. 5-lipoxygenase localized to macrophages, dendritic cells, foam cells, mast cells, and neutrophilic granulocytes, and the number of 5-lipoxygenase expressing cells markedly increased in advanced lesions. By contrast, reticulocyte-type 15-lipoxygenase was expressed at levels that were several orders of magnitude lower than 5-lipoxygenase in both normal and diseased arteries, and its expression could not be related to lesion pathology. Our data support a model of atherogenesis in which 5-lipoxygenase cascade-dependent inflammatory circuits consisting of several leukocyte lineages and arterial wall cells evolve within the blood vessel wall during critical stages of lesion development. They raise the possibility that antileukotriene drugs may be an effective treatment regimen in late-stage disease.
TL;DR: It is demonstrated unequivocally that stratum corneum neutralization alone provokes stratumCorneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.
TL;DR: Simulations demonstrate the usefulness of the time-variant Granger causality for detecting dynamic causal relations within time intervals of less than 100 ms.
TL;DR: No thermo-optical limitations are observed at the extracted /spl sim/35 W/m, therefore such fibers allow scaling to even higher powers, and single transverse mode operation is achieved with a mode-field area of 350 /spl mu/m/sup 2/.
Abstract: We report on a 2.3 m long air-clad ytterbium-doped large-mode-area photonic crystal fiber laser generating up to 80 W output power with a slope efficiency of 78%. Single transverse mode operation is achieved with a mode-field area of 350 µm2. No thermo-optical limitations are observed at the extracted ~35W/m, therefore such fibers allow scaling to even higher powers.
TL;DR: The bulk of the review highlights recent applications of Raman spectroscopy, including structural investigations of a hormone receptor, testing the biocompatibility of dental implants, probing soil components and plant tissue alkaloids, and localization of single bacteria.
Abstract: Although the physics of Raman spectroscopy and its application to purely chemical problems is long established, it offers a noninvasive, nondestructive, and water-insensitive probe to problems in the life sciences. Starting from the principles of Raman spectroscopy, its advantages, and methods for signal enhancement, the bulk of the review highlights recent applications. Structural investigations of a hormone receptor, testing the biocompatibility of dental implants, probing soil components and plant tissue alkaloids, and localization of single bacteria are just four problems in which Raman spectroscopy offers a solution or complements existing methods.
TL;DR: A novel method, based on the angular spectrum of plane waves and coordinate rotation in the Fourier domain, removes geometric limitations posed by conventional propagation calculation and enables us to calculate complex amplitudes of diffracted waves on a plane not parallel to the aperture.
Abstract: A novel method for simulating field propagation is presented. The method, based on the angular spectrum of plane waves and coordinate rotation in the Fourier domain, removes geometric limitations posed by conventional propagation calculation and enables us to calculate complex amplitudes of diffracted waves on a plane not parallel to the aperture. This method can be implemented by using the fast Fourier transformation twice and a spectrum interpolation. It features computation time that is comparable with that of standard calculation methods for diffraction or propagation between parallel planes. To demonstrate the method, numerical results as well as a general formulation are reported for a single-axis rotation.
TL;DR: Increase of activation over time in Broca's area was specific for 'real' language acquisition only, independent of the kind of language.
Abstract: Language acquisition in humans relies on abilities like abstraction and use of syntactic rules, which are absent in other animals. The neural correlate of acquiring new linguistic competence was investigated with two functional magnetic resonance imaging (fMRI) studies. German native speakers learned a sample of 'real' grammatical rules of different languages (Italian or Japanese), which, although parametrically different, follow the universal principles of grammar (UG). Activity during this task was compared with that during a task that involved learning 'unreal' rules of language. 'Unreal' rules were obtained manipulating the original two languages; they used the same lexicon as Italian or Japanese, but were linguistically illegal, as they violated the principles of UG. Increase of activation over time in Broca's area was specific for 'real' language acquisition only, independent of the kind of language. Thus, in Broca's area, biological constraints and language experience interact to enable linguistic competence for a new language.
TL;DR: In this article, a strategy for an environmental risk assessment of chemicals, using a combination of structure-activity relationships (SAR), toxicological and ecotoxicological tests and modelling, is presented.
TL;DR: Interestingly, other parts of the transcriptional program involve novel, IL-3-independent pathways that antagonize differentiation-inducing effects of wild-type Flt3, which should ease the development of specific therapies.
TL;DR: The supramarginal gyrus (left> right) and the dorsolateral cerebellum (lobules V and VI, left>right) were significantly correlated with good task performance and may play a critical role in short-term storage of pitch information and the continuous pitch discrimination necessary for performing this pitch memory task.
TL;DR: In this article, the formation of highly phosphorylated tau, containing a number of PHF-like epitopes in torpor during hibernation, was investigated in the entorhinal cortex, hippocampus and isocortical areas.
Abstract: Neurofibrillary pathology [paired helical filaments (PHFs)] formed by the microtubule-associated protein tau in a hyperphosphorylated form is a major hallmark of Alzheimer's disease and related disorders. The process of tau phosphorylation, thought to be of critical importance for PHF formation, and its potential link to neurodegeneration, however, is not understood very well, mostly because of the lack of a physiological in vivo model of PHF-like tau phosphorylation. Here we describe the formation of highly phosphorylated tau, containing a number of PHF-like epitopes in torpor during hibernation. PHF-like phosphorylation of tau was not associated with fibril formation and was fully reversible after arousal. Distribution of PHF-like tau followed a consistent pattern, being most intense in the entorhinal cortex, hippocampus, and isocortical areas. Within the hippocampus, a particularly high labeling was seen in CA3 pyramidal cells. Somewhat lesser reactivity was present in CA1 neurons while dentate gyrus granule cells were not reactive. Formation of PHF-like tau in CA3 neurons was paralleled by the regression of synaptic contacts of the mossy fiber system terminating on CA3 apical dendrites. Mossy fiber afferentation was re-established during arousal, concomitantly with the decrease of PHF-like tau in CA3 neurons. These findings implicate an essential link between neuronal plasticity and PHF-like phosphorylation of tau. The repeated formation and degradation of PHF-like tau might, thus, represent a physiological mechanism not necessarily associated with pathological effects. Hibernation will, therefore, be a valuable model to study the regulation of PHF-like tau-phosphorylation and its cell biological sequelae under physiological in vivo conditions.
TL;DR: The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.
Abstract: Background— The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. Methods and Results— In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch–like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic loc...
TL;DR: Topical replenishment with epidermal physiologic lipids could represent a potential method to reduce the adverse cutaneous effects of both topical glucocorticoid treatment and Cushing's syndrome, indicating that even short-term exposure to potent glucoc Corticosteroids can exert profound negative effects on cutaneous structure and function.
TL;DR: The vitamin C contents of the tomato products decreased during the thermal processing of tomatoes, and the total phenolics concentration and the water soluble antioxidant capacity increased, while the polyphenol content increased.
Abstract: This study was conducted to investigate the antioxidant vitamin C, the polyphenol content, and the hydrophilic antioxidant capacity of tomato juice, baked tomatoes, tomato sauce, and tomato soup. During the production of tomato juice and during the preparation of the other tomato products, samples were taken after different times, respectively, after each particular production step. High-performance liquid chromatography was used to determine the content of vitamin C. The total phenolics content was analyzed spectrophotometrically by using the Folin-Ciocalteu method. The hydrophilic antioxidant capacity was measured by using three different methods: the Trolox equivalent antioxidant capacity assay, the ferric reducing antioxidant power test, and the photochemiluminescence assay. The vitamin C contents of the tomato products decreased during the thermal processing of tomatoes. In contrast, the total phenolics concentration and the water soluble antioxidant capacity increased.
TL;DR: The enzymatic decellularization process of heart valves revealed a time-dependent loss of cells, ECM components and biomechanical strength, suggesting ECM-integrity may be compromised with prolonged incubation.
TL;DR: A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis, and reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation and are considered to be a key factor in tumour progression.
Abstract: SummaryBackground Solar ultraviolet (UV) radiation is considered to be a major aetiological factor in melanoma and non-melanoma skin cancer. A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis. However, in vivo data for human skin are still lacking. Reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation (LPO) and are considered to be a key factor in tumour progression.
Objectives We hypothesized that in human skin cancer the natural redox balance is disturbed and that this imbalance may result in an accumulation of LPO products.
Methods To test this, skin biopsies of superficial spreading melanoma were compared with age-matched benign melanocytic naevi and young healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each). Expression of the antioxidant enzymes, copper–zinc superoxide dismutase, manganese superoxide dismutase and catalase was analysed by immunohistochemical techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was visualized.
Results In human melanoma biopsies, a significant overexpression of the antioxidant enzymes was found when compared with surrounding non-tumour tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO marker MDA was significantly increased in melanoma tissue. MDA was located not only in typical melanoma cells, but also occurred in surrounding keratinocytes. In contrast, a severely disturbed antioxidant balance with diminished antioxidant enzymes was found in non-melanoma tumours, whereas MDA was elevated only in squamous cell carcinomas.
Conclusions These findings indicate that oxidative stress may play different roles in the pathogenesis of human skin cancers. In non-melanoma skin cancer, a diminished antioxidant defence caused by chronic UV exposure might contribute to multistep carcinogenesis, whereas melanoma cells exhibit increased oxidative stress which could damage surrounding tissue and thus support the progression of metastasis.
TL;DR: Electrophysiological and structural evidence is presented showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain, and identifies a previously unknown role of haem as an acute signalling molecule.
Abstract: Haem is essential for living organisms, functioning as a crucial element in the redox-sensitive reaction centre in haemproteins1. During the biogenesis of these proteins, the haem cofactor is typically incorporated enzymatically into the haem pockets of the apo-haemprotein as the functionally indispensable prosthetic group2,3. A class of ion channel, the large-conductance calcium-dependent Slo1 BK channels, possesses a conserved haem-binding sequence motif. Here we present electrophysiological and structural evidence showing that haem directly regulates cloned human Slo1 channels and wild-type BK channels in rat brain. Both oxidized and reduced haem binds to the hSlo1 channel protein and profoundly inhibits transmembrane K+ currents by decreasing the frequency of channel opening. This direct regulation of the BK channel identifies a previously unknown role of haem as an acute signalling molecule.
TL;DR: Developments in neoadjuvant and adjuvant treatments of colorectal liver metastases that aim to improve the results of surgical management of this disease are examined.
Abstract: Background:
Surgical resection is the only potentially curative treatment for colorectal liver metastases, with 5-year survival rates approaching 40 per cent. However, at present only 20–25 per cent of such lesions are deemed resectable. This review examines developments in neoadjuvant and adjuvant treatments of colorectal liver metastases that aim to improve the results of surgical management of this disease.
Methods:
A literature review was undertaken based on a Medline search from 1970 to May 1998.
Results:
Further evolution in surgical technique is unlikely to lead to a dramatic increase in the resectability rate of colorectal liver metastases. Recent developments in neoadjuvant and adjuvant chemotherapy schedules, together with a range of interventional radiological procedures and interstitial lytic techniques, show promise in terms of extending the limits of resectability and decreasing recurrence rates associated with these lesions. Using multimodality regimens 5-year survival rates of 40 per cent are now being reported for lesions that were initially considered irresectable.
Conclusion:
Patients with colorectal liver metastases should be assessed in units that can offer all the specialist techniques necessary to deliver optimum care. Incorporation of newer neoadjuvant and adjuvant treatments into management strategies should occur in the setting of randomized trials. © 1999 British Journal of Surgery Society Ltd