Localization of human breast-carcinoma xenografts using antibodies to carcinoembryonic antigen.

Affinity-purified antibodies to carcinoembryonic antigen (CEA) have been injected into immune-suppressed mice bearing xenografts of human breast tumours. It has been shown that the antibodies localized in the tumours but not in normal tissues. The degree of tumour localization correlates with the amount of tumour CEA, and is unaffected by levels of circulating CEA or CEA/anti-CEA immune complexes

Rotationally resolved photoelectron spectra in resonance enhanced multiphoton ionization of Rydberg states of NH

Results of combined theoretical and experimental studies of photoelectron spectra resulting from (2+1) resonance enhanced multiphoton ionization (REMPI) via the f ^1Π(3pσ), g ^1Δ(3pπ), and h ^1Σ^+(3pπ) Rydberg states of NH are reported. The overall agreement between these calculated and measured spectra is encouraging. Strong ΔN=N+−N’=even peaks, particularly for ΔN=0, are observed in these spectra. Low‐energy Cooper minima are predicted to occur in the l=2 wave of the kπ(^1Σ^+), kπ(^1Σ^−), and kπ(^1Δ) photoelectron channels for the f state, the kπ(^1Δ), kδ(^1Π), and kδ(^1Φ) channels for the g state, and the kπ(^1Σ^+) and kδ(^1Π) channels for the h state of NH. Depletion of the d wave (l=2) contributions to the photoelectron matrix element in the vicinity of these Cooper minima subsequently enhances the relative importance of the odd l  waves. The observed ΔN transitions are also affected by strong l  mixing in the electronic continuum induced by the nonspherical molecular potential. Interference of continuum waves between degenerate ionization channels also determines the spectral pattern observed for photoionization of the f ^1Π state of NH. Photoelectron angular distributions and the angular momentum compositions of photoelectron matrix elements provide further insight into the origin of these Cooper minima

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

The glycosyltransferase EOGT regulates adropin expression in decidualizing human endometrium

In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the feto-maternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential post-translational modification that links glucose sensing to cellular stress resistance. Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-GlcNAc modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase, OGT) but not the enzyme that removes the modification (O-GlcNAcase, OGA). Notably, EOGT, an endoplasmic reticulum-specific O-GlcNAc transferase that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs. Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions. The most downregulated gene upon EOGT knockdown in decidualizing cells was ENHO, which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index. Taken together, our findings reveal that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points towards a novel mechanistic link between metabolic disorders and adverse pregnancy outcome. [Abstract copyright: Copyright © 2017 Endocrine Society.

Atomistic modelling of large-scale metal film growth fronts

We present simulations of metallization morphologies under ionized sputter deposition conditions, obtained by a new theoretical approach. By means of molecular dynamics simulations using a carefully designed interaction potential, we analyze the surface adsorption, reflection, and etching reactions taking place during Al physical vapor deposition, and calculate their relative probability. These probabilities are then employed in a feature-scale cellular-automaton simulator, which produces calculated film morphologies in excellent agreement with scanning-electron-microscopy data on ionized sputter deposition.Comment: RevTeX 4 pages, 2 figure

Combined chelation therapy in thalassemia major for the treatment of severe myocardial siderosis with left ventricular dysfunction

<p>Abstract</p> <p>Background</p> <p>In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.</p> <p>Methods</p> <p>T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.</p> <p>Results</p> <p>At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006).</p> <p>Conclusion</p> <p>In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.</p> <p>Trial registration</p> <p>This trial is registered as NCT00103753</p

Administering anticipatory medications in end-of-life care: A qualitative study of nursing practice in the community and in nursing homes

Background: In the United Kingdom, an approach to improving end-of-life care has been the introduction of ‘just in case’ or ‘anticipatory’ medications. Nurses are often responsible for deciding when to use anticipatory medications, but little is known about their experiences. Aim: To examine nurses’ decisions, aims and concerns when using anticipatory medications. Design: An ethnographic study in two UK regions, using observations and interviews with nurses working in community and nursing home teams (n = 8). Findings: Observations (n = 83) and interviews (n = 61) with community nurses. Nurses identified four ‘conditions’ that needed to be established before they implemented anticipatory medications: (1) irreversibility; (2) inability to take oral medication; (3) where the patient was able, they should consent and (4) decision had to be independent of demands or requests from patient’s relatives. By using anticipation medications, nurses sought to enable patients to be ‘comfortable and settled’ by provision of gradual relief of symptoms at the lowest dose possible. They aimed to respond quickly to needs, seeking to avoid hospital admission or medical call-out, while adhering to local prescribing policies. Worries included distinguishing between pain and agitation, balancing risks of under- and over-medication and the possibility of hastening death. Conclusion: Nurses take a leading role in the administration of anticipatory medications. Nurses apply consideration and caution to the administration of anticipatory medications but some experience emotional burden. Education, training and experience played a role in the nurses’ confidence and should continue to be central to efforts to improving the quality of palliative care in the community and nursing homes