Plasma neurotensin release and gastric emptying in the dumping syndrome

Seventy-three patients were studied after ingesting a liquid glucose meal, tagged with ¹¹³Indium. Nineteen of these patients were awaiting surgery for their duodenal ulcer, while 54 were studied postoperatively, 25 of whom experienced troublesome postprandial (dumping) symptoms in their daily lives. The radioactive marker emptied significantly faster in the symptomatic patients than in the symptomfree, pre and post-operative groups (initial emptying rate 3.45 ± 0.23, compared with 1.16 ± 0.19 and 1.27 ± 0.15% fall in counts/min respectively; p < 0.01). Initial (20 min) rises in the plasma concentrations of neurotensin-like immunoreactivity measured during the test correlated significantly with the rate of gastric emptying in all patients, being greatest in patients with dumping symptoms. Physiological concentrations of neurotensin have been shown to delay gastric emptying. The excessive rise in plasma neurotensin-like immunoreactivity in patients with dumping symptoms, presumably occuring as a result of the rapid passage of nutrients to the neurotensin-rich ileum, may possibly have a compensatory role in slowing further emptying from the stomach.     

Evidence that the rate of association of adenosine 3'',5''-monophosphate to its chemotactic receptor induces phosphodiesterase activity in Dictyostelium discoideum

Adenosine 3',5'-monophosphate (cyclic AMP) mediates cell aggregation in Dictyostelium discoideum. Cell aggregation is enhanced by pulses of cyclic AMP. Application of pulses of cyclic AMP to cells that were starved only for 1 h (postvegetative cells) induces enzyme activity. One of the enzymes induced by cyclic AMP pulses is phosphodiesterase. We pulsed postvegetative cells with a set of cyclic AMP derivatives that were selected according to certain conformational and physical-chemical properties, and we measured their effect on the induction of phosphodiesterase activity. The cyclic nucleotide specificity for chemotaxis in the aggregative phase was similar to the specificity for phosphodiesterase induction in the postvegetative phase. The shape of the dose-response curves shows a paradox: the activity of a derivative, when applied at receptor-saturating concentrations, is inversely related to its affinity. These results can be explained by the assumption that the response of the chemoreceptor to different cyclic AMP derivatives is proportional to the frequency of associations (rate receptor) and not to the proportion of occupied receptors (occupation receptor). The characteristics of rate receptors and occupation receptors during chemosensory transduction will be discussed.     

Non-transferrin-bound iron species in the serum of hypotransferrinaemic mice.

Serum from homozygous hypotransferrinaemic mice (a mixed group of males and females, aged 6-8 wk) was found to contain low levels of iron (mean 0.9 +/- 0.5 microM (SEM, n = 4), as assayed by conventional serum iron assays. Similarly, low levels of non-transferrin-bound iron were determined with a nitrilotriacetate chelation assay (1.3 +/- 0.4 microM, n = 4) (Singh, S., Hider, R.C. and Porter, J.B. (1990) Analytical Biochemistry 186, 320-323). Mononuclear Fe (citrate) was undectable by electron paramagnetic resonance spectroscopy (EPR). Significantly larger quantities of iron (16 +/- 5 microM, n = 8) were detected by the bleomycin assay (Gutteridge, J.M.C., Rowley, D.A. and Halliwell, B. (1981) Biochemical Journal 199, 263-265), while non-haem iron assay or atomic absorption spectrophotometry revealed up to 96 microM iron. Haemoglobin iron was detectable at approximately 10 microM by spectrophotometry. Ferri-haem was undetectable by EPR spectroscopy. Serum ferritin levels of 641 +/- 128 micrograms/l (n = 14) in hypotransferrinaemic mice (wild-types 44 +/- 6 micrograms/l, n = 14) were observed and these cannot account for the non-transferrin-bound iron. Hypotransferrinaemic mouse serum therefore contains large quantities of non-transferrin-bound iron which is unreactive in some assays used to detect such iron in human iron overload. Fractionation by Sephadex G200 chromatography revealed three distinct species with apparent molecular weights of > or = 150 kDa, 40-80 kDa and 1-5 kDa. The iron may be distinguished from known extracellular iron proteins and haem-proteins by its availability to hot acid extractions.     

Molecular evidence for the rapid propagation of mouse t haplotypes from a single, recent, ancestral chromosome

Mouse t haplotypes are variant forms of chromosome 17 that exist at high frequencies in worldwide populations of two species of commensal mice. To determine both the relationship of t haplotypes to each other and the species within which they exist, 35 representative t haplotypes were analyzed by means of 10 independent molecular probes, including five DNA clones and five polypeptide spots identified by means of two- dimensional gel electrophoresis. All of the tested haplotypes were found to share restriction fragments and polypeptide spots that are absent in mice carrying wild-type forms of chromosome 17. This observation provides the first direct evidence that all of the known t haplotypes are descendents of a single ancestral chromosome. The absence of variation among t haplotypes could mean that this ancestral chromosome existed relatively recently, in which case it would be necessary to postulate introgressions of t haplotypes across species lines to explain their presence in both Mus domesticus and M. musculus. Alternatively, it is possible that the ancestral chromosome existed prior to the split between M. domesticus and M. musculus and that, by chance, our probes fail to detect polymorphisms that exist among the t haplotypes. A further result of our analysis is the characterization of a partial t haplotype in a wild population of Israeli mice.      

The cost of ant attendance and melezitose secretion in the black bean aphid Aphis fabae

1. The aphid Aphis fabae (Scopoli) is facultatively tended by Lasius niger (Linnaeus) ants. Previously, we found that A. fabae colonies can be made up of several clones, and that clones display significant differences in the composition of their honeydew sugars, especially in the amount of the ant attractant sugar melezitose that they produce. 2. These clonal differences could greatly impact the strength of the mutualistic interaction with ants as well as the aphids' fitness. 3. Hence, the aim of this study was to compare the fitness of different A. fabae clones that differed in their melezitose secretion, and whether or not they were tended by ants. 4. Individual fitness indices, colony growth, and alate production of single‐clone aphid colonies were analysed. 5. The results demonstrate that the fitness consequences of ant attendance critically depend on an interaction between levels of melezitose production. In particular, we show that high‐melezitose secreting clones produce fewer alates and hence might have a lower dispersal ability in the presence of ants. 6. Furthermore, these data confirm previous evidence that ant attendance is costly and results in the production of fewer apterae.     

Translational competition by mRNA species encoding albumin, ferritin, haemopexin and globin

The photoreactive gamma-(p-azidoanilidate) analog of ATP, AzAnATP, was used to affinity-label the chloroplastic and cytoplasmic leucyl-tRNA synthetases of Euglena gracilis. The analog is able to replace the substrate ATP in the tRNA leucylation reaction catalyzed by both enzymes. In the presence of ATP, it is a competitive inhibitor against ATP as well as leucine for the two isoenzymes, as is also shown for the photoinactive gamma-anilidate analog of ATP, AnATP, which does not serve as substrate in the enzyme reaction. During ultraviolet irradiation, the enzymes are irreversibly inactivated by AzAnATP in a concentration-dependent and time-dependent manner indicative of photoaffinity labeling. Both ATP and leucine, but not tRNA, protect the enzymes against ultraviolet-induced inactivation by AzAnATP. Comparative kinetic characterization of the inactivation process reveals differences in the active centers of the two intracellular isoenzymes.     

Analysis of bronchoalveolar lavage fluid proteome from systemic sclerosis patients with or without functional, clinical and radiological signs of lung fibrosis

Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained from nine SSc patients with lung fibrosis (SSc_Fib+) with that obtained from six SSc patients without pulmonary fibrosis (SSc_Fib-) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously identified proteins in human BALF, showed no significant variation between SSc_Fib+ patients and SSc_Fib- patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots), and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN were downregulated in SSc_Fib+ patients compared with SSc_Fib- patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2, calumenin, and mtDNA TOP1 in SSc_Fib+ patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins, especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis. Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers of disease.