Cleaved beta 2-microglobulin partially attains a conformation that has amyloidogenic features.

beta(2)-Microglobulin, a small protein localized in serum and on cell surfaces, can adopt specific aggregating conformations that generate amyloid in tissues and joints as a complication to long-term hemodialysis. We characterize a proteolytic variant of beta(2)-microglobulin (cleaved after Lys(58)) that as a trimmed form (Lys(58) is removed) can be demonstrated in the circulation in patients with chronic disease. An unexpected electrophoretic heterogeneity of these two cleaved variants was demonstrated by capillary electrophoresis under physiological conditions. Each separated into a fast and a slow component while appearing homogeneous, except for a fraction of oxidized species detected by other techniques. The two components had different binding affinities for heparin and for the amyloid-specific dye Congo red, and the equilibrium between the two forms was dependent on solvent conditions. Together with analysis of the differences in circular dichroism, the results suggest that beta(2)-microglobulin cleaved after Lys(58) readily adopts two equilibrium conformations under native conditions. In the cleaved and trimmed beta(2)-microglobulin that appears in vivo, the less populated conformation is characterized by an increased affinity for Congo red. These observations may help elucidate why beta(2)-microglobulin polymerizes as amyloid in chronic hemodialysis and facilitate the search for means to inhibit this process.     

Study of the Infectivity of Saline-Stored Campylobacter jejuni for Day-Old Chicks

The culturability of three Campylobacter jejuni strains and their infectivity for day-old chicks were assessed following storage of the strains in saline. The potential for colonization of chicks was weakened during the storage period and terminated 3 to 4 weeks before the strains became nonculturable. The results from this study suggest that the role of starved and aged but still culturable campylobacters may be diminutive, but even more, that the role of viable but nonculturable stages in campylobacter epidemiology may be negligible. Even high levels of maternally derived anti-campylobacter outer membrane protein serum antibodies in day-old chicks did not protect the chicks from campylobacter colonization.     

Observations on the Ecology of Weaver Ants (Oecophylla smaragdina Fabricius) in a Thai Mangrove Ecosystem and Their Effect on Herbivory of Rhizophora mucronata Lam.

Ants of the genus Oecophylla are predators of other insects and are able to protect a variety of terrestrial plants against pest insects; however, observations on the ecology of these ants in mangrove forests are lacking. General observations on the ecology of Oecophylla smaragdina were carried out in a Thai mangrove forest to determine if these ants can protect their host plants in less favorable mangrove habitats. Leaf herbivory and the density of O. smaragdina ants were measured on Rhizophora mucronata trees at two sites. The results showed a negative correlation between ant density and herbivory. At both sites, the mean percent damaged leaf area was more than four times higher on trees without ants compared to “ant‐trees.” A significant negative correlation was found between tree mean percent leaf damage and the density of ants on the tree. Furthermore, on trees with ants, there was less herbivory on leaves close to ant nests compared to other leaves on the tree. Most damage was caused by chrysomelid beetles (62%) and sesarmid crabs (25%) and both types of herbivory were significantly reduced on ant‐trees.     

Soluble Collagen VI Induces Tyrosine Phosphorylation of Paxillin and Focal Adhesion Kinase and Activates the MAP Kinase Erk2 in Fibroblasts

Signals from the extracellular matrix can modulate cellular differentiation and gene expression. We have shown previously that in contrast to other extracellular matrix molecules pepsin-solubilized collagen VI (CVI) can stimulate DNA synthesis of various mesenchymal cell types, apparently independent of integrin-mediated signal transduction. In order to further elucidate collagen VI-induced signaling events, we exposed mouse 3T3 fibroblasts and human HT1080 fibrosarcoma cells to soluble CVI. CVI induced tyrosine phosphorylation of proteins that associate with focal adhesions, such as paxillin, focal adhesion kinase (FAK), and p130CAS. Furthermore, it activated the mitogen-activated protein kinase, erk2. Kinetic analysis showed that these phosphorylations were transient, reaching a maximum after 5 min for transformed HT1080 cells and 30 min for 3T3 fibroblasts. These effects were partly inhibited by a beta1-integrin function blocking antibody and by single chains of CVI. Our results indicate that soluble fragments of native collagen VI, a ubiquitous component of the interstitial extracellular matrix, can mediate stimulation of DNA synthesis via tyrosine phosphorylation of paxillin, FAK, p130CAS, and erk2 in the absence of classical growth factors. Thus, CVI may serve as a matrix-derived sensor that allows for rapid reconstitution of a tissue defect by activating nearby mesenchymal cells.     

Synthesis of novel progestin-rhenium conjugates as potential ligands for the progesterone receptor.

To assist in the development of technetium-based radiopharmaceuticals that are useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have synthesized a series of small-sized metal chelates according to 'n + 1' mixed-ligand, thioether-carbonyl and organometallic designs. In these preliminary investigations, rhenium was used as a model for the radioactive technetium. The metal chelates contain the rhenium metal in several oxidation states, being + 5, + 3, and + 1, and they were attached to 21-substituted progesterone derivatives. A competitive receptor-binding assay (rat uterine cytosol, 0 degrees C) was used to determine the binding affinity of these conjugates for the progesterone receptor. The highest affinity of 9% (RU5020 = 100%) was obtained with a '3 + 1' mixed-ligand complex, containing a NMe group as the central donor atom in the tridentate ligand part. This value reflects a relative binding affinity of 75% compared with the parent steroid progesterone.     

Phenylbutazone,chloramphenicol and mammalian chromosomes

Summary Two potentially myelotoxic agents, phenylbutazone and chloramphenicol, had no cytogenetic effect on human and rat bone-marrow cellsin vivo. Nor was chloramphenicol capable of damaging chromosomes in cultured human lymphocytesin vitro. However, chloramphenicol reduced the proportion of rubidomycin-induced chromatid exchanges in rats in relation to the number of other types of aberrations. The possible relation between the chromosome-damaging and myelotoxic effects of chemical agents is discussed.

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Zusammenfassung Zwei potentiell myelotoxische Agentien — Phenylbutazon und Chloramphenicol — zeigten keine cytogenetische Wirkung auf Knochenmarkszellen von Mensch und Ratte in vivo. Chloramphenicol ließ auch die Fähigkeit vermissen, Chromosomen menschlicher Lymphocyten in vivo zu schädigen. Chloramphenicol reduzierte jedoch den Anteil Rubidomycin-induzierter Chromatiden-Reunionen bei Ratten im Vergleich zu der Anzahl anderer Aberrationen. Es wird die mögliche Beziehung zwischen der chromosomenschädigenden und der myelotoxischen Wirkung chemischer Stoffe diskutiert.

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This work has been supported by a grant from Anders Hasselbalch's fond til leukæmiens bekæmpelse.     

A unique variant of streptococcal group O-antigen (C-polysaccharide) that lacks phosphocholine.

Streptococcus mitis strain SK598, which represents a subgroup of biovar 1, possesses a unique variant of the C-polysaccharide found in the cell wall of all strains of Streptococcus pneumoniae and in some strains of S. mitis. This new variant lacks the choline methyl groups in contrast to the previously characterized forms of C-polysaccharide, which all contain one or two choline residues per repeat. The following structure of the repeating unit of the SK598 polysaccharide was established: where AAT is 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose. This structure is identical to the double choline-substituted form of C-polysaccharide, except that it is substituted with ethanolamine instead of choline. This extends the number of recognized C-polysaccharide variants to four.     

Energy gain and energy gap in normal-weight children: longitudinal data of the KOPS

Population-based prevention of overweight needs evidence-based goals consistent with our present knowledge about energy gap (i.e., daily imbalance between energy intake and energy expenditure resulting in overweight). Longitudinal data of normal-weight children (1,029 girls and 1,028 boys; Kiel Obesity Prevention Study, KOPS) were used to calculate energy gain (i.e., increase in fat mass (FM) and fat-free mass (FFM)) in normal-weight children staying normal weight (persistent children) or becoming overweight (incident children). Taking into account weight gain in proportion to height gain (normal development) energy gap was calculated from increases in FM and FFM exceeding normal development. Children were divided into two groups and were followed from age 6 to 10 (group A) and 10 to 14 years (group B). FM and FFM were measured. Medians of 4-year BMI- (kg/m(2))/weight changes (kg) were +1.8/+13.2 (A) and +3.0/+18.7 (B) in girls, and +1.6/+12.8 (A) and +2.6/21.7 (B) in boys. Corresponding data for FM/FFM (kg) were +3.1/+10.2 (A) and +5.1/12.7 (B) in girls, and +2.3/10.8 (A) and +3.0/18.6 (B) in boys. The 4-year-incidence of overweight (%) were 9.4 (A) and 5.4 (B) in girls, and 11.0 (A) and 3.8 (B) in boys, respectively. Mean energy gains (kcal/day) were 26.8 (A) and 46.4 (B) in girls, and 22.1 (A) and 32.5 (B) in boys. The 90th percentile of energy gap (kcal/day) in incident children were 58.1 (A) and 72.0 (B) in girls and 46.0 (A) and 53.2 (B) in boys. To prevent overweight in children energy gap should not exceed 46-72 kcal/day.