Translation and ribosome assembly in extremely thermophilic archaebacteria.

Several features of translation and ribosome structure in extremely thermophilic, sulfur-dependent archaebacteria are described, including: i) a peculiar mechanism of transfer RNA-mediated 70S ribosome formation from free subunits; ii) poly(U)translation by hybrid ribosomes composed by one archaebacterial and one eucaryotic subunit; iii) ribosome assembly and homologous and heterologous RNA/protein recognition.     

Structure and biological activity of crustacean gastrointestinal peptides identified with antibodies to gastrin/cholecystokinin.

Four gastrin/cholecystokinin-like peptides (G/CCK) which cross-react with a specific C-terminal gastrin/CCK antiserum have been isolated from the stomach of the marine crustacean Nephrops norvegicus. The molecular weight of the four peptides was estimated between 1000 and 2000 Da by molecular sieving. By radioimmunoassay, the cross-reactivity of these peptides with human gastrin 17-I was found to be around 0.03%. Pure peptidic fractions were recovered after four successive steps of HPLC. Amino-acid analysis suggested a similarity between the four peptides identified which may belong to a new family. A limited homology between the C-terminus of one Nephrops peptide and vertebrate G/CCK was found after sequencing. Two of the peptides exhibited secretagogue effects on crustacean isolated midgut glands. The Nephrops peptides, although structurally distinct from the vertebrate G/CCKs, appear to serve similar biological functions in crustaceans.     

Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease.

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.     

Induction of DNA bending by bifunctional intercalating agents of the 7H-pyridocarbazole family

The structures and binding energetics of selected complexes formed between the deoxynucleotides d(CpGpGpCpG).d(CpGpCpCpG), d(CpGpApTpCpG)2, d(GpCpGpCpCpG).d(CpGpGpCpGpC), and d(CpGpCpCpCpG)2 with the DNA bifunctional intercalating agent ditercalinium and three of its rigid linking chain derivatives have been investigated theoretically by means of a molecular mechanics approach that takes into account nucleic acid flexibility, ligand flexibility and solvent dielectric effects (R. Lavery, in: Unusual DNA structures, eds S. Harvey and R. Wells (Pergamon, New York, 1988) p. 189; R. Lavery, in: DNA bending and curvature, eds W.K. Olson et al. (Adenine Press, New York, 1988) p. 191). The piperidinium chains of the bis-intercalating ligands are always located in the major groove of DNA. For the energy-minimized complexes the ligand proceeds to bind following preferentially the 5'-pyrimidine-purine-3' alternating sequence, thus dictating the number of internal exclusion sites. The complexes with three exclusion sites will present (i) a bending of the structure towards the major groove, and (ii) a non-ideal distribution of unwinding angles; complexes with less than three exclusion sites will remain essentially linear. The absence of a bend does not preclude other types of local deformations of the base-pairs such as inclination, buckle and tip. The proposed structures of the d(CpGpApTpCpG)2 complexes are in agreement with NMR structural results. The possible relevance of these findings to a previously proposed mode of interaction for ditercalinium-like DNA ligands is discussed.