Glove Dressing for Initial Management of Hand Burns.

Initial hand dressings for burned hands should be compatible with preservation of skin substitutes and grafts, splinting, and active motion. We have developed a standardized glove dressing directed at these requirements. Early experience with this glove dressing has included feasible clinical application, 7- to 10-minute application time, and 90% preservation of total active range of motion in a normal hand placed in the dressing under test conditions.

Design, synthesis, and biological evaluation of hydroquinone derivatives as novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase.

Analogues of the compound 2,5-di-tert-butylhydroquinone (BHQ) are capable of inhibiting the enzyme sarco/endoplasmic reticulum ATPase (SERCA) in the low micromolar and submicromolar concentration ranges. Not only are SERCA inhibitors valuable research tools, but they also have potential medicinal value as agents against prostate cancer. This study describes the synthesis of 13 compounds representing several classes of BHQ analogues, such as hydroquinones with a single aromatic substituent, symmetrically and unsymmetrically disubstituted hydroquinones, and hydroquinones with omega-amino acid tethers attached to their hydroxyl groups.

Structure-based virtual screening for novel inhibitors of the sarco/endoplasmic reticulum calcium ATPase and their experimental evaluation.

A public compound library with 260,000 compounds was screened virtually by computational docking for novel inhibitors of the transmembrane enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). Docking was performed with the program GOLD in conjunction with a high resolution X-ray crystal structure of SERCA. Compounds that were predicted to be active were tested in bioassays.

Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test.

Objective: To test the efficacy of the low-dose glucagon test in assessing adrenal gland function.

Study Design: Subcutaneous glucagon was used to assess the hypothalamo-pituitary-adrenal gland (HPA) axis in 215 healthy children. Concordance of this test with the low-dose intravenous ACTH test was established for 42 children.

Intercalated cytosine motif and novel adenine clusters in the crystal structure of the Tetrahymena telomere.

The cytosine-rich strand of the Tetrahymena telomere consists of multiple repeats of sequence d(AACCCC). We have solved the crystal structure of the crystalline repeat sequence at 2.5 A resolution.

Solution structures of the individual single strands of the fragile X DNA triplets (GCC)n.(GGC)n.

Three-dimensional structures of the fragile X triplet repeats (GCC)n and (GGC)n are derived by using one- dimensional/two-dimensional NMR. Under a wide range of solution conditions (10-150 mM NaCl,pH6-7)(GCC)5-7 strands form exclusively slipped hairpins with a 3' overhanging C. The slipped hairpins of (GCC)n strands show the following structural characteristics: (i) maximization of Watson-Crick G.

Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications.

Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC)n.(GCC)n, are correlated with the ability of the individual G- and C-rich single strands to form hairpin structures. Two-dimensional NMR and gel electrophoresis studies show that both the G- and C-rich single strands form hairpins under physiological conditions.

Extension of the four-stranded intercalated cytosine motif by adenine.adenine base pairing in the crystal structure of d(CCCAAT).

The crystal structure of d(CCCAAT), refined at 2.0 A resolution, shows a four stranded molecule in which two parallel duplexes intercalate with opposite polarity, using cytosine.protonated cytosine base pairs.

Stable loop in the crystal structure of the intercalated four-stranded cytosine-rich metazoan telomere.

In most metazoans, the telomeric cytosine-rich strand repeating sequence is d(TAACCC). The crystal structure of this sequence was solved to 1.9-A resolution.

Enzymatic elongation of microsatellite oligomers for use in direct-label chemiluminescent hybridizations.

Short, synthetic oligonucleotide sequences representing microsatellites and other short tandem repeats can be elongated (concatamerized) using a simple method in which complementary strands are annealed, phosphorylated, primer extended and ligated. When used in direct-label chemiluminescent hybridizations, the elongated microsatellite sequences provide an approximately 30-fold increase in signal strength compared with microsatellite oligomers that have not been concatamerized. Concatamerization of simple repeat oligomers further enables the use of relatively short oligonucleotide sequences in direct-label chemiluminescent hybridization experiments, thereby reducing the overall need for radioisotopes in certain commonly performed laboratory procedures such as DNA fingerprinting and selection of clones containing microsatellite sequences.

Crystal structure of intercalated four-stranded d(C3T) at 1.4 A resolution.

The crystal structure of d(C3T), solved at 1.4 A resolution, reveals that the molecule forms a four-stranded intercalated complex. It consists of two parallel-stranded duplexes, each of which is held together by cytosine-protonated cytosine base pairs.

Evidence from CD spectra that d(purine).r(pyrimidine) and r(purine).d(pyrimidine) hybrids are in different structural classes.

CD spectra and difference CD spectra of four d(oligopurine).r(oligopyrimidine) and four r(oligopurine).d(oligopyrimidine) hybrid duplexes containing mixed A.

Unusual structures of the tandem repetitive DNA sequences located at human centromeres.

The presence of the highly conserved repetitive DNA sequence d(AATGG)n.d(CCATT)n in human centromeres argues for a special role for this sequence in recognition, most probably through the formation of an unusual structure during mitosis. Quantitative one- and two-dimensional nuclear magnetic resonance (1D/2D NMR) spectroscopic studies reveal that the Watson-Crick duplex d(AATGG)n.

Sequence-dependent conformational variations in the B-DNA double-helix of poly d(AATT).poly d(AATT).

X-ray diffraction data from well oriented and polycrystalline fibers of the lithium salt of poly d(AATT).poly d(AATT) are isomorphous with those from B-DNA. The double-helix consists of conformationally identical antiparallel strands and the molecular symmetry is 2 5(2); the asymmetric unit is a tetranucleotide, AATT, and 5 tetranucleotides span two turns per strand.

Crystal structure of four-stranded Oxytricha telomeric DNA.

The sequence d(GGGGTTTTGGGG) from the 3' overhang of the Oxytricha telomere has been crystallized and its three-dimensional structure solved to 2.5 A resolution. The oligonucleotide forms hairpins, two of which join to make a four-stranded helical structure with the loops containing four thymine residues at either end.

Highly conserved repetitive DNA sequences are present at human centromeres.

Highly conserved repetitive DNA sequence clones, largely consisting of (GGAAT)n repeats, have been isolated from a human recombinant repetitive DNA library by high-stringency hybridization with rodent repetitive DNA. This sequence, the predominant repetitive sequence in human satellites II and III, is similar to the essential core DNA of the Saccharomyces cerevisiae centromere, centromere DNA element (CDE) III. In situ hybridization to human telophase and Drosophila polytene chromosomes shows localization of the (GGAAT)n sequence to centromeric regions.

CD evidence that the alternating purine-pyrimidine sequence poly[d(A-C).d(G-T)], but not poly[d(A-T).d(A-T)], undergoes an acid-induced transition to a modified secondary conformation.

Circular dichroism and UV absorption data showed that poly[d(A-C).d(G-T)] (at 0.01M Na+ (phosphate), 20 degrees C) underwent two reversible conformational transitions upon lowering of the pH.

The vacuum UV CD bands of repeating DNA sequences are dependent on sequence and conformation.

CD spectra were obtained for eight synthetic double-stranded DNA polymers down to at least 175 nm in the vacuum uv. Three sets of sequence isomers were studied: (a) poly[d(A-C).d(G-T)] and poly[d(A-G).

A.T and C.C+ base pairs can form simultaneously in a novel multistranded DNA complex.

Previous experiments have established that in certain synthetic oligomeric DNA sequences, including mixtures of d(AACC)5 with d(CCTT)5, adenine-thymine (A.T) base pairs form to the exclusion of neighboring protonated cytosine-cytosine (C.C+) base pairs [Edwards, E.

High-speed DNA sequencing: an approach based upon fluorescence detection of single molecules.

We are developing a laser based technique for the rapid sequencing of large fragments (approximately 40 kb) of DNA based upon the detection of single, fluorescently tagged nucleotides cleaved from a single DNA fragment. We have demonstrated significant progress on several of the important steps of this technique. The projected rate of sequencing is several hundred bases per second which is orders of magnitude faster than existing methods.

Conservation of the human telomere sequence (TTAGGG)n among vertebrates.

To determine the evolutionary origin of the human telomere sequence (TTAGGG)n, biotinylated oligodeoxynucleotides of this sequence were hybridized to metaphase spreads from 91 different species, including representative orders of bony fish, reptiles, amphibians, birds, and mammals. Under stringent hybridization conditions, fluorescent signals were detected at the telomeres of all chromosomes, in all 91 species. The conservation of the (TTAGGG)n sequence and its telomeric location, in species thought to share a common ancestor over 400 million years ago, strongly suggest that this sequence is the functional vertebrate telomere.