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Results for “Enhancer mapping”

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At least 469 records · Page 26Linked to original sources

PubMed2000

Definition of a T-cell receptor beta gene core enhancer of V(D)J recombination by transgenic mapping.

V(D)J recombination in differentiating lymphocytes is a highly regulated process in terms of both cell lineage and the stage of cell development. Transgenic and knockout mouse studies have demonstrated that transcriptional enhancers from antigen receptor genes play an important role in this regulation by activating cis-recombination events. A striking example is the T-cell receptor beta-chain (TCRbeta) gene enhancer (Ebeta), which in the mouse consists of at least seven nuclear factor binding motifs (betaE1 to betaE7). Here, using a well-characterized transgenic recombination substrate approach, we define the sequences within Ebeta required for recombination enhancer activity. The Ebeta core is comprised of a limited set of motifs (betaE3 and betaE4) and an additional previously uncharacterized 20-bp sequence 3' of the betaE4 motif. This core element confers cell lineage- and stage-specific recombination within the transgenic substrates, although it cannot bypass the suppressive effects resulting from transgene integration in heterochromatic centromeres. Strikingly, the core enhancer is heavily occupied by nuclear factors in immature thymocytes, as shown by in vivo footprinting analyses. A larger enhancer fragment including the betaE1 through betaE4 motifs but not the 3' sequences, although active in inducing germ line transcription within the transgenic array, did not retain the Ebeta recombinational activity. Our results emphasize the multifunctionality of the TCRbeta enhancer and shed some light on the molecular mechanisms by which transcriptional enhancers and associated nuclear factors may impact on cis recombination, gene expression, and lymphoid cell differentiation.

Animals↗

PubMed1987

The sequence motifs that are involved in SV40 enhancer function also control SV40 late promoter activity.

The simian virus 40 (SV40) enhancer element is constituted of two domains which contain sequences important for late transcription (M. Ernoult-Lange, F. Omilli, D. O'Reilly and E. May, J. Virol. 61, 167-176, 1987). By analysing a series of clustered point mutations generated throughout the enhancer region we mapped domain I from nt 232 to 272 and domain II from nt 184 to 216. These two domains which are required for late promoter activity both in the presence and in the absence of T antigen correspond closely to the domains B and A respectively, identified for enhancer function (M. Zenke, T. Grundström, H. Matthes, M. Wintzerith, C. Schatz, A. Wildeman and P. Chambon, EMBO J., 5, 387-397, 1986). Similarly to the enhancer function the late promoter elements defined by these two domains contain multiple sequence motifs. Moreover there is a striking overlap between the sequence motifs within domain A, active for early enhancer function and those within domain II involved in efficient late transcription.

Animals↗

PubMed1996

Segmental expression of Hoxa-2 in the hindbrain is directly regulated by Krox-20.

The hindbrain is a segmented structure divided into repeating metameric units termed rhombomeres (r). The Hox family, vertebrate homologs of the Drosophila HOM-C homeotic selector genes, are expressed in rhombomere-restricted patterns and are believed to participate in regulating segmental identities. Krox-20, a zinc finger gene, has a highly conserved pattern of expression in r3 and r5 and is functionally required for their maintenance in mouse embryos. Krox-20 has been shown to directly regulate the Hoxb-2 gene and we wanted to determine if it was involved in regulating multiple Hox genes as a part of its functional role. Hoxa-2 is the only known paralog of Hoxb-2, and we examined the patterns of expression of the mouse Hoxa-2 gene with particular focus on r3 and r5 in wild type and Krox-20-/- mutant embryos. There was a clear loss of expression in r3, which indicated that Hoxa-2 was downstream of Krox-20. Using transgenic analysis with E. coli lacZ reporter genes we have identified and mapped an r3/r5 enhancer in the 5' flanking region of the Hoxa-2 gene. Deletion analysis narrowed this region to an 809 bp Bg/II fragment, and in vitro binding and competition assays with bacterially expressed Krox-20 protein identified two sites within the enhancer. Mutation of these Krox-20 sites in the regulatory region specifically abolished r3/r5 activity, but did not affect neural crest and mesodermal components. This indicated that the two Krox-20 sites are required in vivo for enhancer function. Furthermore, ectopic expression of Krox-20 in r4 was able to transactivate the Hoxa 2/lacZ reporter in this rhombomere. Together our findings suggest that Krox-20 directly participates in the transcriptional regulation of Hoxa-2 during hindbrain segmentation, and is responsible for the upregulation of the r3 and r5 domains of expression of both vertebrate group 2 Hox paralogs. Therefore, the segmental phenotypes in the Krox-20 mutants are likely to reflect the role of Krox-20 in directly regulating multiple Hox genes.

Animals↗

PubMed1997

Template convolution to enhance or detect structural features in macromolecular electron-density maps.

A conceptually simple real-space convolution method has been developed which can be used to detect or enhance structural features in experimental macromolecular electron-density maps. The method has been implemented in a computer program (ESSENS). One application of the method is in selectively visualizing secondary-structure elements in multiple isomorphous replacement (MIR) maps of proteins, prior to map interpretation. This application is demonstrated for MIR maps of P2 myelin protein [Jones, Bergfors, Sedzik & Unge (1988). EMBO J. 7, 1597-1604; Cowan, Newcomer & Jones (1993). J. Mol. Biol. 230, 1225-1246] and glyoxalase I [Cameron, Olin, Ridderström, Mannervik & Jones (1997). In preparation]. Another application is in finding the optimal orientation and position of a known structural fragment (e.g. a protein domain or a ligand) in any type of electron-density map (real-space or phased molecular replacement). This application is demonstrated for the complex of acetylcholinesterase and the snake toxin fasciculin II [Harel, Kleywegt, Ravelli, Silman & Sussman (1995). Structure, 3, 1355-1366] where the toxin was located in a map phased using the molecular-replacement solution for the acetylcholinesterase alone.

Journal Article↗

PubMed2001

GPS computer navigators to shorten EMS response and transport times.

GPS (global positioning satellite system to determine one's position on earth) units have become inexpensive and compact. The purpose of this study is to assess the effectiveness of a GPS enhanced computer street map navigator to improve the ability of EMS drivers in an urban setting to locate their destination and shorten response times. For part I, residential addresses in the city were randomly selected from a telephone directory. Two driver/navigator teams were assigned to drive to the address adhering to speed limits. One team used a standard street map, whereas the other team used a GPS computer navigator. The travel time and distance of the runs were compared. For part II, the computer GPS navigator was placed on an ambulance to supplement their normal methods of navigation to find the address requesting EMS. After the run was completed, EMS providers were interviewed to determine their opinion of whether the GPS navigator was helpful. For part I the results showed that in the 29 initial test runs, comparing the GPS team versus the standard map team, the mean distances traveled were 8.7 versus 9.0 kilometers (not significant) and the mean travel times were 13.5 versus 14.6 minutes (P=.02), respectively. The GPS team arrived faster in 72% runs. For part II the results showed that most EMS providers surveyed noted that the GPS computer navigator enhanced their ability to find the destination and all EMS providers acknowledged that it would enhance their ability to find a destination in an area in which they were unfamiliar. These results suggest that a portable GPS computer navigator system is helpful and can enhance the ability of prehospital care providers to locate their destination. Because these units are accurate and inexpensive, GPS computer navigators may be a valuable tool in reducing pre-hospital transport times.

Ambulances↗

PubMed2006

Inhibition of p38 MAP kinase in the early posttransplantation phase redistributes blood vessels from the surrounding stroma into the transplanted endocrine tissue.

Transplanted pancreatic islets attain a chronically decreased vascular density following transplantation, despite the increased concentrations of vascular endothelial growth factor (VEGF) secreted from beta-cells in response to hypoxia during culture and in the immediate posttransplantation phase. VEGF, however, exerts dual effects on endothelial cells, and in islet endothelial cells of the adult, the vascular permeability-inducing effects of VEGF seem normally more pronounced than those to induce angiogenesis. p38 MAP kinase activity has recently been shown to serve as a switch to separate these properties of VEGF; inhibition of p38 MAP kinase activity enhances VEGF-induced angiogenesis and, at the same time, abrogates VEGF-induced vascular permeability. We hypothesized that the revascularization of transplanted islets may be hampered by a predisposition of adult islet endothelial cells to react to VEGF by forming fenestrae rather than migrating and proliferating. We therefore administered the p38 MAP kinase inhibitor SB203580 by daily IP injections for the first 14 days following transplantation, and then studied the influence of this treatment on the oxygen tension, blood perfusion, and vascular density of the islet grafts 1 month posttransplantation. SB203580 treatment redistributed islet graft blood vessels from the stroma into the endocrine tissue, and this redistribution of blood vessels into the endocrine tissue was accompanied by an increased oxygenation of the islet cells. However, the total number of blood vessels in the tissue was not affected. The blood perfusion of the islet grafts was also similar in control and SB203580-treated animals. Our results suggest that effects of VEGF to preferentially induce vascular permeability may partially contribute to, but is not the main cause of, low revascularization of transplanted islets.

Animals↗

PubMed2000

Matrix metalloproteinase-1 expression by interaction between monocytes and vascular endothelial cells.

There is accumulating evidence of complicated interactions among vascular cells, i.e. endothelial cells, smooth muscle cells and monocytes/macrophages, in the regulation of vascular function and remodeling. We have investigated the mechanisms responsible for matrix metalloproteinase (MMP)-1 expression by interactions between monocytes and vascular endothelial cells. THP-1 cells (human monocytic cell line) and human umbilical vein endothelial cells (HUVECs) were cocultured. MMP-1 levels in the culture medium were measured by enzyme-linked immunosorbent assays. Collagenolytic activity in the culture medium was measured by fluorescence labeled-collagen digestion. Immunohistochemistry using an anti-MMP antibody was carried out to determine which types of cell produce MMP-1. The addition of THP-1 cells to HUVECs for 48 h induced increases in MMP-1 levels and collagenolytic activity, which were 5- and 2-fold relative to those of HUVECs alone, respectively. A separate coculture experiment revealed that direct contact of THP-1 cells and HUVECs contributed to enhanced MMP-1 production in the cocolture. Immunohistochemical analysis revealed that both types of cell produce MMP-1 in the coculture. Neutralizing anti-interleukin-1 beta and tumor necrosis factor- alpha antibodies inhibited MMP-1 production by the coculture. The Src kinase and MEK inhibitors significantly inhibited MMP-1 production by the coculture. Coculture of THP-1 cells and HUVECs induced significant increases in Src and mitogen activated protein (MAP) kinase activities. Enhanced MMP-1 expression induced by monocyte-endothelial cell interactions may play an important role in the pathogenesis of atherosclerosis and plaque rupture.

Arteriosclerosis↗

PubMed2025

Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs.

The Qinghai-Tibet Plateau, characterized by its extreme environmental conditions, presents significant challenges to life, making it an ideal region for studying adaptation and evolution. Tibetan pigs, known for their high genetic diversity and exceptional adaptability to high altitudes, serve as excellent models for investigating high-altitude adaptation. While previous studies have extensively identified genetic determinants associated with high-altitude adaptation, the molecular mechanisms, particularly cis-regulatory patterns, remain poorly understood. Here, we conducted a selective sweep analysis using 484 genomes from Chinese and Western pig breeds across various altitudes, revealing 38.56 Mb of genomic regions under selection in Tibetan pigs. Enrichment analysis identified the lung as the primary functional tissue involved in high-altitude adaptation, supported by tissue-specific transcriptional and regulatory patterns observed between Tibetan and Meishan pigs (low altitude). By integrating genomic, RNA-seq, ATAC-seq, and H3K27ac HiChIP data, we constructed comprehensive enhancer-promoter regulatory maps of candidate genes and pinpointed promising genetic determinants associated with high-altitude adaptation, including SNPs in EPAS1, KLF13, SPRED1, and CFD. These loci were predicted to influence chromatin accessibility and the interactions of regulatory elements, with altered binding strength of relevant transcription factors. Further in vitro experiments confirmed that these loci function as allele-specific enhancers, modulating the expression of target genes. Our findings elucidate the regulatory basis of high-altitude adaptation in Tibetan pigs and provide valuable insights for exploring hypoxia-related diseases in livestock and humans.

Animals↗

PubMed1992

MAP kinase is constitutively activated in gip2 and src transformed rat 1a fibroblasts.

Rat 1a fibroblasts transformed by the Gi2 oncogene, gip2, exhibit a constitutively elevated mitogen-activated protein (MAP) kinase activity that correlates with enhanced tyrosine phosphorylation of the p42 MAP kinase polypeptide. The MAP kinase activity in gip2 transformed cells is 50-60% of the pertussis toxin-sensitive, thrombin-stimulated activity observed in wild-type Rat 1a cells. A similar activation of MAP kinase is observed in src but not ras or raf transformed Rat 1a cells, indicating that the persistent MAP kinase activity results from the action of the specific oncoprotein and is not the consequence of cellular transformation. The enhanced transactivation function of c-Jun characteristic of the transformed phenotype, measured using a collagenase promoter-CAT reporter gene, is observed in gip2, src, ras, and raf transformed Rat 1a cells. The regulatory networks controlled by the four transforming oncogenes therefore alter the activity of specific transcription factors, but only gip2 and src constitutively activate MAP kinase. The findings demonstrate that the catalytic activity of growth factor-regulated cytoplasmic kinases are selectively and stably activated as a consequence of specific oncogene expression.

Animals↗

PubMed2002

[Effects of chronic alcohol administration on changes of extracellular dopamine and serotonin concentration induced by methamphetamine--comparison of two different alcohol preference rat lines].

We have investigated the effects of single administration of methamphetamine (MAP) (1.0 mg/kg, i.p.), and of combined administration of ethanol (EtOH) (2.0 g/kg, i.v.) and MAP (1.0 mg/kg, i.p.) on striatal extracellular dopamine (DA) and serotonin (5-HT) levels in chronic alcohol treated rats using a brain-microdialysis method. We used two different lines of rats with high and low alcohol preferences, (high alcohol preference rat (HAP) and low alcohol preference rat (LAP), respectively), which were chronically fed an alcohol containing liquid diet for 6 to 8 weeks. The percent change in DA and 5-HT in striatum following single administration of MAP was significantly higher in control-fed LAP than HAP. However, in the alcohol-fed group, the percent changes in DA and 5-HT were significantly elevated in the alcohol-fed HAP compared to LAP. There were no significant increases in striatal extracellular DA and 5-HT in alcohol-fed LAP. In combined administration of MAP and EtOH, extracellular DA and 5-HT levels increased slightly following EtOH administration in chronic alcohol-fed rats, especially in HAP. Dramatic increases of DA and 5-HT levels were observed in alcohol-fed HAP following EtOH and MAP administration. The percent change in DA and 5-HT in alcohol-fed HAP was further elevated to 4667.7 +/- 1095.5% and 3116.9 +/- 1162.7% of the maximal change, respectively. These percent changes ware higher than that observed with a single administration of MAP. Meanwhile, LAP were less sensitive to the influence of chronic EtOH administration and to single administration of MAP. These results demonstrate that a chronic treatment of EtOH enhances the sensitivity to MAP in a high alcohol preference rat line, when two drugs were administrated simultaneously, and that a significant difference of responsiveness to abused drugs was indicated between these two lines. It is necessary to consider the alcohol preference when investigating the interaction of alcohol and/or other abused drugs.

Alcoholism↗

PubMed2002

The jury is out on "guilt by association" trials.

The availability of comprehensive protein-protein interaction maps will significantly enhance medical research and aid the functional characterisation of novel genes. To date, the largest scale studies of protein-protein interactions have used the yeast two hybrid method. In this review we take a closer look at the different approaches used in these studies and discuss some key considerations that should be taken into account when designing high throughput interaction mapping projects.

Genome↗

PubMed2006

Enhancement of anti-inflammatory tendency by SB203580, p38alpha specific inhibitor, in human fibroblast-like synoviocyte cell line, MH7A.

Interleukin-1 beta (IL-1beta) is an abundant cytokine, which, together with TNF-alpha, mediates inflammatory events in rheumatoid arthritis (RA). IL-1beta is known to induce the induction of inflammatory cytokines and metalloproteinases (MMPs) in rheumatoid synovial cells. Here, we assessed these inflammatory events by measuring IL-1beta levels in the human synovial cell line, MH7A. We observed that the activation of p38 MAP kinase by IL-1beta was involved in the induction of inflammatory cytokines, as well as several genes, including MMP-1 and MMP-3. SB203580, a specific p38 MAP kinase inhibitor, inhibited the production of IL-1beta-induced cytokines and MMPs, while the levels of the tissue inhibitor of metalloproteinase (TIMPs) were unchanged by treatment with SB203580. Moreover, the induction of suppressor of cytokine signaling 3 (SOCS3) and interferon regulatory factor 1 (IRF-1) were both found to be induced by the inhibition of p38 MAP kinase. Therefore, we suggested that the inhibition of p38 MAP kinase might enhance anti-inflammatory tendencies in the MH7A cells.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1992

Chromatographic resolution and characterization of a nerve growth factor-dependent kinase that phosphorylates microtubule-associated proteins 1 and 2 in PC12 cells.

When the supernatant fractions from extracts of control and nerve growth factor (NGF)- or dibutyryl cyclic AMP-treated PC12D cells were applied to DEAE-Sepharose columns and proteins were eluted with a gradient of NaCl, three separate peaks of kinase activity that phosphorylated microtubule-associated proteins (MAPs) were recovered. Enhancement of the kinase activity in peak 1 was noted in the case of dibutyryl cyclic AMP-treated cells. In contrast, the kinase activity in the third peak was markedly elevated, in terms of the ability to phosphorylate MAP1 and MAP2, in the case of the extract from NGF-treated cells. This activity was designated previously as NGF-dependent MAP kinase. The apparent molecular mass of the active kinase was 45-50 kDa. The apparent Km value was 35 microM for ATP with either MAP1 or MAP2 as substrate. When the kinase activity in the fractions from the DEAE-Sepharose column was assayed in the presence of Mn2+ instead of Mg2+, another NGF-stimulated kinase activity was detected in the fractions eluted by a lower concentration of NaCl than that which eluted the Mg(2+)-activated kinase. Other growth factors, namely, epidermal growth factor and basic fibroblast growth factor, also stimulated the activity of NGF-dependent MAP kinase. Possible involvement of the kinase in the outgrowth of neurites has been suggested. The NGF-induced activation of NGF-dependent MAP kinase was blocked by the presence of K-252a. In contrast, the activation of NGF-dependent MAP kinase by basic fibroblast growth factor and by epidermal growth factor was not blocked, but actually stimulated by K-252a, a result that correlates well with the analogous actions of the drug on the outgrowth of neurites that is induced by these growth factors. The latter observation strengthens the possibility of a close relationship between the outgrowth of neurites and the activation of NGF-dependent MAP kinase.

Animals↗

PubMed2006

Feasibility and measurement precision of 3D quantitative blood flow mapping of the prostate using dynamic contrast-enhanced multi-slice CT.

We have developed a 3D dynamic contrast-enhanced (DCE) multislice CT protocol that covers the complete prostate. The DCE-CT data are subsequently analysed using the adiabatic approximation of the tissue homogeneity model resulting in five 3D quantitative maps of blood flow, mean transit time, extraction fraction, extracellular extravascular space and delay time. The purpose of this study was to establish the feasibility of determining these parameters in the prostate with a spatial resolution as high as approximately 0.1 cc as well as a good measurement precision. The precision of the parameter estimation as a function of noise level is determined by a Monte Carlo-based method that simulates the effect of noise present in the data. We find that the precision depends on the value of the flow and transit time, where a higher value is favourable. At a noise level of 4 HU in combination with a peak enhancement in the iliac arteries of approximately 300 HU the 95% confidence intervals are sufficiently small to discriminate whether a parameter value is above or below a given threshold. We have collected and analysed the noise level in the DCE-data of five patients. A noise level of 3.8 HU on average can be obtained by averaging to a voxel volume of 4.5 x 4.5 x 5 mm(3) = 0.1 cc. Analysis of the parameter maps shows that it is feasible to detect both small and large lesions, as well as irregularly shaped lesions.

Contrast Media↗

PubMed2006

Is the risk for secondary cancers after proton therapy enhanced distal to the Planning Target Volume? A two-case report with possible explanations.

It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors.

Animals↗

PubMed2006

Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas.

UNLABELLED: 3'-Deoxy-3'-fluorothymidine (FLT), a thymidine analog, is under investigation for monitoring cellular proliferation in gliomas, a potential measure of disease progression and response to therapy. Uptake may result from retention in the biosynthetic pathway or leakage via the disrupted blood-tumor barrier. Visual analysis or static measures of 18F-FLT uptake are problematic as transport and retention cannot be distinguished. METHODS: Twelve patients with primary brain tumors were imaged for 90 min of dynamic 18F-FLT PET with arterial blood sampling. Total blood activity was corrected for labeled metabolites to provide an FLT input function. A 2-tissue compartment, 4-rate-constant model was used to determine blood-to-tissue transport (K1) and metabolic flux (K(FLT)). Modeling results were compared with MR images of blood-brain barrier (BBB) breakdown revealed by gadolinium (Gd) contrast enhancement. Parametric image maps of K1 and K(FLT) were produced by a mixture analysis approach. RESULTS: Similar to prior work with 11C-thymidine, identifiability analysis showed that K1 (transport) and K(FLT) (flux) could be estimated independently for sufficiently high K1 values. However, estimation of K(FLT) was less robust at low K1 values, particularly those close to normal brain. K1 was higher for MRI contrast-enhancing (CE) tumors (0.053 +/- 0.029 mL/g/min) than noncontrast-enhancing (NCE) tumors (0.005 +/- 0.002 mL/g/min; P < 0.02), and K(FLT) was higher for high-grade tumors (0.018 +/- 0.008 mL/g/min, n = 9) than low-grade tumors (0.003 +/- 0.003 mL/g/min, n = 3; P < 0.01). The flux in NCE tumors was indistinguishable from contralateral normal brain (0.002 +/- 0.001 mL/g/min). For CE tumors, K1 was higher than K(FLT). Parametric images matched region-of-interest estimates of transport and flux. However, no patient has 18F-FLT uptake outside of the volume of increased permeability defined by MRI T1+Gd enhancement. CONCLUSION: Modeling analysis of 18F-FLT PET data yielded robust estimates of K1 and K(FLT) for enhancing tumors with sufficiently high K1 and provides a clearer understanding of the relationship between transport and retention of 18F-FLT in gliomas. In tumors that show breakdown of the BBB, transport dominates 18F-FLT uptake. Transport across the BBB and modest rates of 18F-FLT phosphorylation appear to limit the assessment of cellular proliferation using 18F-FLT to highly proliferative tumors with significant BBB breakdown.

Adult↗

PubMed2004

Nano-optics with single quantum systems.

This paper reviews the recent progress in using single quantum systems, here mainly single fluorescent molecules, as local probes for nano-optical field distributions. We start by discussing the role of the absorption cross-section for the spatial resolution attainable in such experiments and its behaviour for different environmental conditions. It is shown that the spatial distribution of field components in a high-numerical aperture laser focus can be mapped with high precision using single fluorescent molecules embedded in a thin polymer film on glass. With this proof-of-principle experiment as a starting point, the possibility of mapping strongly confined and enhanced nano-optical fields close to material structures, e.g. sharp metal tips, is discussed. The mapping of the spatial distribution of the enhanced field at an etched gold tip using a single molecule is presented as an example. Energy transfer effects and quenching are identified as possible artefacts in this context. Finally, it is demonstrated that the local quenching at a sharp metal structure nevertheless can be exploited as a novel contrast mechanism for ultrahigh-resolution optical microscopy with single-molecule sensitivity.

Fluorescence Resonance Energy Transfer↗

PubMedDate not supplied

Growth factors and nutrients in the short bowel syndrome.

Massive intestinal resection often results in long-term dependence on parenteral nutrition (TPN). In an effort to enhance bowel rehabilitation, the amino acid glutamine, growth hormone and a diet optimized to enhance absorption have been administered to >300 patients with the short bowel syndrome. Initially about 60% of the patients were weaned from TPN and an additional 30% had reduced TPN requirements. At long-term follow up (2 years) 40% of the group remained off TPN, 40% had reduced TPN requirements, and 20% had the same requirements. This report addresses issues such as the optimization of diet and provides a care map which should enhance the rehabilitation of patients with the short bowel syndrome.

Adaptation, Physiological↗