Efimov physics in heteronuclear four-body systems.

We study three- and four-body Efimov physics in a heteronuclear atomic system with three identical heavy bosonic atoms and one light atom. We show that exchange of the light atom between the heavy atoms leads to both three- and four-body features in the low-energy inelastic rate constants that trace to the Efimov effect. Further, the effective interaction generated by this exchange can provide an additional mechanism for control in ultracold experiments. Finally, we find that there is no true four-body Efimov effect-that is, no infinite number of four-body states in the absence of two- and three-body bound states-resolving a decades-long controversy.

Acute caffeine ingestion: clinical features in patients attending the emergency department and Scottish poison centre enquiries between 2000 and 2008.

BACKGROUND AND AIMS: Little information is available regarding the healthcare burden associated with deliberate caffeine ingestion. The present study sought to establish the impact of caffeine ingestion on hospital attendances and Poisons Centre enquiries in Scotland. METHODS: Retrospective analyses of clinical data from patients attending the Royal Infirmary of Edinburgh after acute caffeine ingestion, and TOXBASE enquiries from Scotland regarding caffeine poisoning between 2000-2008 inclusive. Cochran-Armitage trend tests were used to evaluate changes in annual admissions and TOXBASE enquiries. RESULTS: There were 43 hospital attendances due to deliberate caffeine ingestion, representing 0.2% of all poisoning cases. The median (interquartile range) stated dose was 1040 mg (600-1500 mg). Minor gastrointestinal symptoms were common, and no patient developed features of severe toxicity. There were 1418 enquiries to TOXBASE concerning caffeine poisoning, representing 0.2% of all poisoning enquiries from Scotland. The proportions of hospital admissions and TOXBASE enquiries due to caffeine ingestion have remained constant. CONCLUSION: Caffeine ingestion is uncommon, and results in only a small number of hospital attendances and Poisons Centre enquiries. In contrast to patterns reported elsewhere, the prevalence of caffeine abuse has not increased in Scotland over recent years.

Anaemia as a risk stratification tool for symptomatic patients referred via the two-week wait pathway for colorectal cancer.

Introduction Anaemia is associated with cancer. In 2014 a new form was introduced in our department requesting a haemoglobin (Hb) result on every two-week wait referral for suspected colorectal cancer (CRC). The aim of this study was to review the impact of this intervention. In particular, the significance of any evidence of anaemia (without additional indices) was investigated. Methods A review was conducted of 1,500 consecutive suspected CRC referrals recorded prospectively over a 10-month period. Data on demographics, referral Hb, referral criteria and outcomes were analysed. Anaemia was defined according to World Health Organization criteria (Hb <120g/l for women, Hb <130g/l for men). Results Overall, 1,015 patients were eligible for inclusion in the study. Over a third (38.2%) were documented as anaemic on referral. These patients were three times more likely to be diagnosed with CRC than non-anaemic patients (odds ratio [OR]: 3.22, 95% confidence interval [CI]: 1.87-5.57). Using a more stringent threshold (Hb <100g/l for women and <110g/l for men), they were four times more likely to have CRC (OR: 4.27, 95% CI: 2.35-7.75). Almost a quarter (23.7%) were actually anaemic at the time of referral but not referred with anaemia. In this subgroup, there was a 2.8-fold increase in risk of CRC diagnosis compared with non-anaemic patients (adjusted OR: 2.77, 95% CI: 1.55-4.95). Conclusions Nearly a quarter of patients not referred with iron deficiency anaemia had evidence of anaemia and this was still associated with a higher rate of CRC detection. A full blood count alone might help to risk stratify symptoms such as change in bowel habit in patients on urgent pathways and identify those cases most likely to benefit from invasive investigation.

Pattern of lithium exposure predicts poisoning severity: evaluation of referrals to a regional poisons unit.

BACKGROUND: Lithium toxicity may result in severe clinical features. There is on-going uncertainty about the significance of serum lithium concentrations in patients with lithium toxicity. AIM: To examine potential relationships between stated quantity of lithium ingested, serum lithium concentrations, and poisoning severity among patients referred to a regional poisons centre. METHODS: Prospective evaluation of enquiries to the Scottish Poisons Information Bureau about lithium toxicity between 2000-2005 inclusive. RESULTS: There were 172 enquiries, relating to acute ingestion (n = 101), acute-on-therapeutic ingestion (n = 38), or chronic poisoning (n = 33). Poisoning severity was moderate or severe in 9.9%, 26.3% (p < 0.05 vs. acute) and 54.5% (p < 0.005 vs. acute) of each group, respectively. Median (IQR) serum lithium concentrations in each group were: 2.4 (1.7-3.3) mmol/l, 2.1 (1.4-3.8) mmol/l, and 2.3 (1.9-3.3) mmol/l, respectively. The median stated quantities ingested in acute and acute-on-therapeutic lithium exposure were 5000 mg (2000-11 050 mg) and 4000 mg (2400-8820 mg), respectively. DISCUSSION: Patients with acute-on-therapeutic and chronic poisoning are at greatest risk of severe toxicity. These differences cannot be explained by either the quantity of lithium ingested or serum lithium concentration alone.

Pharmacogenomics and nutrigenomics: synergies and differences.

The success of the Human Genome Project and the spectacular development of broad genomics tools have catalyzed a new era in both medicine and nutrition. The terms pharmacogenomics and nutrigenomics are relatively new. Both have grown out of their genetic forbears as large-scale genomics technologies have been developed in the last decade. The aim of both disciplines is to individualize or personalize medicine and food and nutrition, and ultimately health, by tailoring the drug or the food to the individual genotype. This review article provides an overview of synergies and differences between these two potentially powerful science areas. Individual genetic variation is the common factor on which both pharmacogenomics and nutrigenomics are based. Each human is genetically (including epigenetics) unique and phenotypically distinct. One of the expectations of both technologies is that a wide range of gene variants and related single-nucleotide polymorphism will be identified as to their importance in health status, validated and incorporated into genotype based strategies for the optimization of health and the prevention of disease. Pharmacogenomics requires rigorous genomic testing that will be regulated and analyzed by professionals and acted on by medical practitioners. As further information is obtained on the importance of the interaction of food and the human genotype in disease prevention and health, pharmacogenomics can provide an opportunity driver for nutrigenomics. As we move from disease treatment to disease prevention, the two disciplines will become more closely aligned.

The effect of cyclic nucleotides and protein phosphorylation on calcium permeability and binding in the sarcoplasmic reticulum.

In the absence of cyclic nucleotides heart microsomes have two classes of calcium binding sites with binding constants of 0.69 and 0.071 micron-1 and capacities of 2.2 and 9.7 nmol/mg protein, respectively. Neither cyclic AMP nor monobutyryl cyclic AMP affect binding but cyclic GMP and monobutyryl cyclic GMP cause the complete loss of the high affinity calcium binding sites, Cyclic GMP (but not monobutyryl cyclic GMP) also causes a decrease in the binding constant of the low affinity binding sites. AMP, GMP and Tris-butyrate do not affect calcium binding. The effects of the cyclic nucleotides are direct and are not mediated by protein phosphorylation. Phosphorylation of microsomal proteins increases the binding constant but not the capacity of the high affinity calcium binding sites. The capacity and also, perhaps, binding constant of the low affinity sites is also increased by phosphorylation. In additon to their effects on calcium binding the cyclic nucleotides also affect the movements of calcium into and out of the microsomes. The effects are again direct and not mediated by protein phosphorylation. Cyclic GMP decreases the rate of Ca2+ efflux from preloaded cardiac microsomes and also appears to decrease the rate of uptake of Ca2+ by cardiac microsomes though this effect is less clear cut than the action on efflux. The cyclic nucleotide has a half maximal effect at a concentration of 100 microns. By contrast cyclic AMP increases the rate of influx of Ca2+ into heart microsomes and the rate of efflux of Ca2+ from preloaded preparations. The effect is, however, rather slight. It is suggested that the most obvious interpretation of these results is that cyclic GMP decreases the Ca2+ permeability of the cardiac microsomal membrane while cyclic AMP increases the permeability. In contrast to the results found with membrane preparations from certain other tissues phosphorylation of cardiac microsomal proteins does not appear to alter Ca2+ efflux or influx out of, or into, cardiac microsomal preparations. It is thus concluded that phosphorylation of cardiac microsomal proteins does not affect the Ca2+ permeability of the microsomal membrane.

A Plant Chloroplast Glutamyl Proteinase.

A glutamyl proteinase was partially purified from Percoll gradient-purified spinach (Spinacia oleracea) chloroplast preparations and appeared to be predominantly localized in the chloroplast stroma. The enzyme degraded casein, but of the 11 synthetic endopeptidase substrates tested, only benzyloxycarbonyl-leucine-leucine-glutamic acid-[beta]-napthylamide was hydrolyzed at measurable rates. In addition, the enzyme cleaved the oxidized [beta]-chain of insulin after a glutamic acid residue. There was no evidence that native ribulose-1,5-bisphosphate carboxylase/oxygenase was cleaved by this proteinase. The apparent Km for benzyloxycarbonyl-leucine-leucine-glutamic acid-[beta]NA at the pH optimum of 8.0 was about 1 mM. Cl-ions were required for both activity and stability. Of the proteinase inhibitors covering all four classes of the endopeptidases, only 4-(2-aminoethyl)-benzenesulfonyl-fluoride HCl and L-1-chloro-3-[4-tosylamido]-4-phenyl-2-butanone significantly inhibited the proteinase. The partially purified enzyme had a molecular weight of about 350,000 to 380,000, based on size-exclusion chromatography. The enzyme has both similar and distinctive properties to those of the bacterial glutamyl proteinases. To our knowledge, this is the first description of a plant glutamyl proteinase found predominantly or exclusively in the chloroplast.

Wounding induces a series of closely related trypsin/chymotrypsin inhibitory peptides in leaves of tobacco.

Wounding of tobacco (Nicotiana tabacum) leaves induced the expression of acid-stable trypsin/chymotrypsin inhibitory activity. Analysis by gel filtration determined that the inhibitory activity was contained within a fraction with a native M(r) of ca 5-7 x 10(3). Using ion-exchange column chromatography, this was resolved further into two major fractions, each of which inhibited both trypsin and chymotrypsin. Reverse-phase HPLC identified a total of six peptides from both fractions and each was purified to homogeneity. Four of these peptides inhibited both trypsin and chymotrypsin, a fifth inhibited trypsin only, while the sixth inhibited chymotrypsin almost exclusively. Sequencing of the N-terminal revealed that each peptide had an identical amino acid sequence and that these proteins are similar to a series of trypsin/chymotrypsin inhibitory peptides that are expressed predominantly in the stigmas of Nicotiana alata flowers.

A cysteine proteinase inhibitor purified from apple fruit.

A cysteine proteinase inhibitor has been purified from immature fruit of Malus domestica (var. Royal Gala). The M(r) of this apple cystatin is estimated to be 10,700 by MALDI-TOF mass spectrometry, 11 300 by SDS-PAGE and 11,000 by gel filtration. It is a relatively strong inhibitor of papain with a Ki value of 0.21 nM and also inhibits ficin and bromelain but not cathepsin B. An amino acid sequence was obtained from a peptide produced by trypsin digestion of the inhibitor. Comparison with other plant sequences shows a high degree of homology with other phytocystatins. As the single cysteine proteinase inhibitor detectable in immature apple fruit (5-8 mm diameter), levels of 83.3 pmol/g FW were determined. In larger fruit (up to 16 mm diameter) significantly less inhibitor was present (6.9 pmol/g FW). Given these low levels, it is postulated that this inhibitor has an endogenous role in apple fruit development rather than one of protection against pest or microbial attack.

A method to distinguish between chemical shift and susceptibility effects in NMR microscopy and its application to insect larvae.

We propose a simple method of distinguishing Zeeman broadening arising from susceptibility inhomogeneity and chemical shift variation, applicable to NMR microscopy. The method is based on the use of a specially built probe-head in which orthogonal sample alignment is possible using the same radiofrequency (RF) coil. This allows the investigation of alignment effects in image distortion and relies on the fact that the isotropic chemical shift is invariant under reorientation, whereas the susceptibility-related local field will depend strongly on relative orientation of bounding surfaces with the external polarizing field. We apply this approach to the study of a simple phantom, and an insect larva (Spodoptera litura Fabricius), demonstrating in the latter case that susceptibility variations are sufficiently small to allow chemical shift imaging on a scale greater than 1 ppm.

Fistula-in-ano in infancy and childhood.

The authors report the results of a retrospective study of 36 patients with fistula-in-ano (FIA) and/or perianal abscess (PA) presenting during a 3-year period. In 76.2% of the 21 patients with FIA, the fistulae developed in the first 2 years of life. For eight of the 16 patients who underwent fistulectomy, histological examination of the excised fistulae showed an epithelial lining of the tract mixed with stratified squamous, transitional and columnar epithelium. The early onset of FIA, the high percentage of bilateral and multiple fistulae, and the presence of these types of epithelium lining support a congenital etiology of FIA in children. In boys, a causal relationship exists between PA and FIA.

Decreased expression of fibulin-4 in aortic wall of aortic dissection.

In this research, we will examine the expression of Fibulin-4 in aortic wall to find out its role in aortic dissection development. The samples of aortic wall were obtained from 10 patients operated for acute ascending aortic dissection and five patients for chronic ascending aortic dissection. Another 15 pieces of samples from patients who had coronary artery bypass were as controls. The aortic samples were stained with aldehyde magenta dyeing to evaluate the arrangement of elastic fibers. The Fibulin-4 protein and mRNA expression were both determined by Western blot and realtime quantitative polymerase chain reaction. Compared with the control group, both in acute and chronic ascending aortic dissection, elastic fiber fragments increased and the expression of fibulin-4 protein significantly decreased (P= 0.045 < 0.05). The level of fibulin-4 mRNA decreased in acute ascending aortic dissection (P= 0.034 < 0.05), while it increased in chronic ascending aortic dissection (P=0.004 < 0.05). The increased amounts of elastic fiber fragments were negatively correlated with the expression of fibulin-4 mRNA in acute ascending aortic dissection. In conclusion, in aortic wall of ascending aortic dissection, the expression of fibulin-4 protein decreased and the expression of fibulin-4 mRNA was abnormal. Fibulin-4 may play an important role in the pathogenesis of aortic dissection.

Regulation of Soybean Net Photosynthetic CO(2) Fixation by the Interaction of CO(2), O(2), and Ribulose 1,5-Diphosphate Carboxylase.

Kinetic properties of soybean net photosynthetic CO(2) fixation and of the carboxylase and oxygenase activities of purified soybean (Glycine max [L.] Merr.) ribulose 1, 5-diphosphate carboxylase (EC 4.1.1.39) were examined as functions of temperature, CO(2) concentration, and O(2) concentration. With leaves, O(2) inhibition of net photosynthetic CO(2) fixation increased when the ambient leaf temperature was increased. The increased inhibition of CO(2) fixation at higher temperatures was caused by a reduced affinity of the leaf for CO(2) and an increased affinity of the leaf for O(2). With purified ribulose 1,5-diphosphate carboxylase, O(2) inhibition of CO(2) incorporation and the ratio of oxygenase activity to carboxylase activity increased with increased temperature. The increased O(2) sensitivity of the enzyme at higher temperature was caused by a reduced affinity of the enzyme for CO(2) and a slightly increased affinity of the enzyme for O(2). The similarity of the effect of temperature on the affinity of intact leaves and of ribulose 1,5-diphosphate carboxylase for CO(2) and O(2) provides further evidence that the carboxylase regulates the O(2) response of photosynthetic CO(2) fixation in soybean leaves. Based on results reported here and in the literature, a scheme outlining the stoichiometry between CO(2) and O(2) fixation in vivo is proposed.Oxygen competitively inhibited carboxylase activity with respect to CO(2), and CO(2) competitively inhibited oxygenase activity with respect to O(2). Within the limits of experimental error, the Michaelis constant (CO(2)) in the carboxylase reaction was identical with the inhibition constant (CO(2)) in the oxygenase reaction, and the Michaelis constant (O(2)) in the oxygenase reaction was identical with the inhibition constant (O(2)) in the carboxylase reaction. The Michaelis constant, (ribulose 1,5-diphosphate) was the same in both the carboxylase and oxygenase reactions. This equality of kinetic constants is consistent with the notion that the same enzyme catalyzes both reactions.

Cyclic AMP increase the Na+ permeability of the avian erythrocyte membrane by a process which does not involve protein phosphorylation.

Preparations of avian erythrocyte plasma membranes have been made which are in the form of sealed vesicles. Using these preparations the permeability of the membranes to N+, K+, Mg2+ and Ca2+ was measured. Monobutyryl cyclic AMP and cyclic AMP increased the permeability to Na+ and Ca+ under conditions where no protein phosphorylation could occur. The only effect of phosphorylation of membrane proteins was to reduce Ca+ permeability. It is thus concluded that cyclic AMP increases Na+ permeability in the avian erythroycte by a direct effect which does not involve protein phosphorylation.