Cytogenetic analysis of human solid tumors by in situ hybridization with a set of 12 chromosome-specific DNA probes

We have applied fluorescent in situ hybridization (FISH) to assess the presence of numerical chromosome aberrations in fresh specimens of human solid tumors of varying histology. For this purpose, a set of 12 biotinylated chromosome-specific, repetitive alpha-satellite DNA probes (for chromosomes 1, 6, 7, 9, 10, 11, 15, 16, 17, 18, X and Y) were hybridized directly to isolated interphase nuclei. Utilizing this approach, we found numerical chromosome changes in all tumors. FISH ploidy profiles were in accordance with flow cytometric DNA histograms of these tumor cells.     

Collagens as multidomain proteins

The number of proteins known to contain collagen-like triple helical domains is rapidly increasing. The functions of these domains are to provide molecular rods that separate spatially non-triple helical domains with varied properties and structures and to permit lateral interactions between molecules. Two-thirds of the amino acids of the triple helical domains have their side-chains at the surface of the protein. The triple helix is also a structure that is easily predictable from the primary structure. The structure of several recently discovered collagens are discussed in terms of domains and functions. The triple helical domains have sizes varying from 33 to over 1,000 amino acid residues. The longest uninterrupted triple helices are involved in the formation of the classical quarter-staggered fibrils. Other triple helical domains permit varied molecular aggregates. A very broad spectrum of non-triple helical or globular domains are interspersed by triple helices. Only those located at the extremities of the molecules are large in size, sometimes several hundred kDa, while the domains separating 2 triple helices are small (less than 50 amino acids) and provide the molecules with hinges, proteolytic cleavage sites or other specialized functions like a glycosaminoglycan attachment site. If the assembly of the 3 chains required for the triple helix formation can be controlled in vitro, collagen-like molecules offer an as yet unexploited potential for protein engineering.     

Surface properties of fibrinogen and fibrin

By contact angle measurements on layers of fibrinogen and fibrin, it can be shown that the transformation from fibrinogen to fibrin is accompanied by a change in surface properties from very hydrophilic (fibrinogen) to moderately but definitely hydrophobic (fibrin). It is also shown that, contrary to serum albumin and gamma globulin, fibrinogen does not become more hydrophobic upon drying.     

Search for polythionates in cultures of Chromatium vinosum after sulfide incubation

Cultures of Chromatium vinosum, devoid of sulfur globules, were supplemented with sulfide and incubated under anoxic conditions in the light. The concentrations of sulfide, polysulfides, thiosulfate, polythionates and elemental sulfur (sulfur rings) were monitored for 3 days by ion-chromatography and reversed-phase HPLC. While sulfide disappeared rapidly, thiosulfate and elemental sulfur (S₆, S₇ S₈ rings) were formed. After sulfide depletion, the concentration of thiosulfate decreased fairly rapidly, but elemental sulfur was oxidized very slowly to sulfate. Neither polysulfides (S _x ^2– ), polythionates (S_nO ₆ ^2– , n=4–6), nor other polysulfur compounds could be detected, which is in accordance with the fact that sulfide-grown cells were able to oxidize polysulfide without lag. The nature of the intracellular sulfur globules is discussed.     

A predictive model for life expectancy curves

Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable.     

Analysis of a disease transmission model in a population with varying size

An S I R S epidemiological model with vital dynamics in a population of varying size is discussed. A complete global analysis is given which uses a new result to establish the nonexistence of periodic solutions. Results are discussed in terms of three explicit threshold parameters which respectively govern the increase of the total population, the existence and stability of an endemic proportion equilibrium and the growth of the infective population. These lead to two distinct concepts of disease eradication which involve the total number of infectives and their proportion in the population.Partially supported by NSF Grant No. DMS-8703631. This work was done while this author was visiting the University of VictoriaResearch supported in part by NSERC A-8965     

Synthesis of well-defined phosphate-methylated DNA fragments: the application of potassium carbonate in methanol as deprotecting reagent.

A new deprotection procedure in the synthesis of (partially) phosphate-methylated oligodeoxynucleotides has been developed, involving treatment of fully protected DNA fragments with methanolic potassium carbonate. It is shown that base deprotection can be accomplished in potassium carbonate/methanol without affecting the methyl phosphotriesters. This methodology enables us to synthesize, both in solution and on a solid support, DNA fragments which are phosphate-methylated at defined positions. The solid phase synthesis, however, turns out to be accompanied by considerable demethylation of the phosphotriesters. It is demonstrated that this demethylation does not occur during the deprotection or work-up procedure. Furthermore, it was found that the latter side-reaction is suppressed when the standard capping procedure with acetic anhydride is included.