Effects of in vivo exposure to antineoplastic drugs on DNA repair and replication in human lymphocytes

In peripheral blood lymphocytes of 12 nurses and 3 patients exposed to antineoplastic drugs we determined the ability to repair DNA after UV irradiation and DNA replicative synthesis after stimulation by PHA. In nurses the levels of unscheduled DNA synthesis and DNA replication were not different than in a control group, whereas in patients significant changes were observed during and after chemotherapy in the level of both types of DNA synthesis.     

Recent coral facies of the Indian Ocean Coast of Somalia with an interim check list of corals

Summary From a study of two areas, Jesira and the Bajuni Archipelago, about 400 km apart, a general pattern can be established for the Recent facies, together with the morphological and taxonomic features of the corals. Present day coral development is characterized by true fringing reefs in the Bajuni Archipelago and by scattered patches and knolls in the Jesira area. The coral fauna, consisting of 27 genera and 63 species so far (including all uncertainties, but not sight records), is rather poor, though coral communities are locally well developed. These figures probably reflect incomplete study and sampling. Although comparison with other areas may therefore be premature, a preliminary biogeographical analysis suggests that this fauna is more closely related to that of the Red Sea than to East Africa and the Seychelles. This differs from other published biogeographical work on Indian Ocean coral faunas, but further study of the corals in this and neighbouring areas of the Indian Ocean is needed in order to resolve this apparent anomaly.     

ELECTRON MICROSCOPY OF OSTEOCLASTS IN HEALING FRACTURES OF RAT BONE

Osmium-fixed, undecalcified, callus tissue from healing fractures of rat tibias was sectioned with a diamond knife for study with the electron microscope. Large multinucleated cells were found adjacent to bone. A characteristic labyrinthine infolded border was consistently seen in parts of the cells close to the bone surface. The innermost parts of this "ruffled border" gave rise to vacuoles. The bone surface was always disrupted under the "ruffled border" of the cells. Needle-like crystals were seen at the osseous fringe, within folds in the ruffled border as well as within vacuoles deeper in the cells. Collagen fibers denuded of crystals were never observed. Mitochondria, containing clusters of fine granules, were abundant. The part of the cell away from bone contained rough endoplasmic reticulum and the cell membrane was thrown into irregular microvilli. These observations are discussed in relation to current concepts of osteoclastic resorption of bone.     

The deactivation pathways of the excited-states of the mycosporine-like amino acids shinorine and porphyra-334 in aqueous solution.

In vitro studies on the structurally related mycosporine-like amino acids (MAAs) porphyra-334 and shinorine in aqueous solutions were carried out aiming at their full photochemical and photophysical characterization and expanding the evidence on the assigned UV-photoprotective role of the molecules in vivo. The experiments on shinorine confirmed a high photostability and a poor fluorescence quantum yield, in concordance with previous results on porphyra-334. The estimation of triplet production quantum yields for both MAAs was achieved by laser-flash photolysis measurements. In particular, photosensitization experiments on porphyra-334 support the participation of the triplet state in the photodecomposition mechanism yielding a more precise value of [capital Phi](T). As well, photoacoustic calorimetry experiments allowed the first direct quantification of the nonradiative relaxation pathways of the excited MAAs in solution, corroborating that the vast majority (ca. 97%) of the absorbed energy is promptly delivered to the surroundings as heat, consistently with the low photodecomposition and emission yields observed.     

Ionic iridium-gold and rhodium-gold perfluorobenzenethiolato binuclear complexes: syntheses and solution behavior

By reacting [(C₅Me₅)M(SR_F)₂] (forM = Ir, Rf = C₆F₅ (1a) or C₆F₄H-p (1b); for M = Rh, Rf = C₆F₅ (2a) or C₆F₄H-p (2a)) in toluene with Na[AuCl₄], ionic binuclear compounds with the general formula [(C₅Me₅)M(μ-SR_F)₂AuCl₂]Cl for M = Ir, R = C₆F₅ (3a) or C₆F₄H-p (3a); for M = Rh, R_F = C₆F₅ (4a) or C₆F₄H-p (4b) can be obtained, together with small amounts of [(C₅Me₅)₂Rh₂(μ-SR_F)(μ-Cl)₂]Cl (R_F = C₆F₅ (5a) or C₆F₄H-p (5b)) as by-products when 2a and 2b were used.     

Goldfish cones secrete a two-repeat interphotoreceptor retinoid-binding protein

Vitamin A and fatty acids are critical to photoreceptor structure, function, and development. The transport of these nutrients between the pigment epithelium and neural retina is mediated by interphotoreceptor retinoid-binding protein (IRBP). IRBP, a 133-kDa (human) glycolipoprotein, is the major protein component of the extracellular matrix separating these two cell layers. In amphibians and mammals, IRBP consists of four homologous repeats of about 300 amino acids which form two retinol and four fatty acid-binding sites. Here we show that IRBP in teleosts is a simpler protein composed of only two repeats. Western blot analysis shows that goldfish IRBP is half the size (70 kDa) of IRBP in higher vertebrates. Metabolic labeling studies employing Brefeldin A taken together with in situ hybridization studies and the presence of a signal peptide show that goldfish IRBP is secreted by the cone photoreceptors. The translated amino acid sequence has a calculated molecular weight of 66.7 kDa. The primary structure consists of only two homologous repeats with a similarity score of 52.5%. The last repeats of human and goldfish IRBPs are 69.1% similar with hydrophobic regions being the most similar. These data suggest that two repeats were lost during the evolution of the ray-finned fish (Actinopterygii), or that the IRBP gene duplicated between the emergence of bony fish (Osteichthyes) and amphibians. Acquisition of a multirepeat structure may reflect evolutionary pressure to efficiently transport higher levels of hydrophobic molecules within a finite space. Quadruplication of an ancestral IRBP gene may have been an important event in the evolution of photoreceptors in higher vertebrates. Correspondence to: F. Gonzalez-Fernandez     

Synthesis and biological evaluation of novel NK-1 tachykinin receptor antagonists: The use of cycloalkyl amino acids as a template

In the course of a program aimed at synthesizing novel, potent NK-1 tachykinin receptor antagonists, we developed upon a bioactive model by comparing the low energy structures of a series of peptide and nonpeptide Substance P antagonists. The comparison was based on the super imposition of the aromatic rings, assuming that the rest of the molecule behaves predominantly as a template to arrange the key aromatic groups in the right spatial position. A series of 2-aminocyclohexane carboxylic acid analogues were then selected as the best templates for reproducing the postulated bioactive structure, leading to several pseudo-peptides with interesting biological activity. According to the molecular modeling, these compounds exhibit a neat parallel facing of the indolyl and naphthyl groups at about 3 Å distance. Ultraviolet absorption and steady state fluorescence measurements support this conclusion, showing a linear correlation between the spectral properties and the binding affinity of these analogues. Stacking of the indole ring with naphthalene gives rise to a complex characterized by a well-defined molar extinction coefficient. Consistently, steady state and lifetime fluorescence measurements suggest that the quenching process is ascribable to ground-state interactions between the chromophores. Implications of the π stacking propensity of aromatic groups in the biological activity of the compounds examined are briefly discussed. © 1995 John Wiley & Sons, Inc.     

Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase: exon skipping, insertion of duplicate sequence, and missense mutations leading to the deficiency of the pyruvate dehydrogenase complex.

Human pyruvate dehydrogenase (PDH)-complex deficiency is an inborn error of metabolism that is extremely heterogeneous in its presentation and clinical course. In a study of 14 patients (7 females and 7 males), we have found a mutation in the coding region of the E1 alpha gene in all 14 patients. Two female patients had the same 7-bp deletion at nt 927; another female patient had a 3-bp deletion at nt 931. Another female patient was found to have a deletion of exon 6 in her cDNA. Two other female patients were found to have insertions, one of 13 bp at nt 981 and one of 46 bp at nucleotide 1078. Two male patients were found to have a 4-bp insertion at nucleotide 1163. The remaining six patients all had missense mutations. A male patient and a female patient both had an A1133G mutation. The other missense mutations were C214T, C615A, and C787G (two patients). Five of these mutations are novel mutations, five have been previously reported in other patients, and two were published observations in other patients in an E1 alpha-mutation summary. In the four cases where parent DNA was available, only one mother was found to be a carrier of the same mutation as her child.