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W J Cook

Publications and source records attributed to W J Cook.

89 records · Page 5Linked to original sources

Conformational flexibility in single-stranded oligonucleotides: crystal structure of a hydrated calcium salt of adenylyl-(3'--5')-adenosine.

The crystal and molecular structure of a hydrated calcium salt of adenylyl-(3'--5')-adenosine(ApA) was determined from X-ray diffraction data collected on an automated diffractometer. Crystals of the salt are orthorhombic, space group P21212, with a = 30.614 (3), b = 17.894 (2), and c = 5.373 (1) A. The structure was solved by a combination of Patterson and direct methods and refined by least squares. The final value of the R index is 0.08. The 5'-terminal adenosine residue has a C(2')-endo ribose and assumes a syn conformation, which is stabilized by an O(5')-H...N(3) hydrogen bond within the nucleoside. The 3'-terminal nucleoside has a C(3')-endo ribose and is in the anti conformation. Both omega and omega', the torsion angles within the phosphodiester group, are approximately 60 degrees. Adenine bases from adjacent anions are joined by pairs of N(6)-H...N(1) hydrogen bonds and are stacked with symmetry-related bases. The calcium ion is bound to the dinucleoside phosphate by a direct interaction with the phosphate group and by outer-sphere, ligand-mediated interactions with O(2') of the 5'-terminal nucleoside and N(7) of the 3'-terminal nucleoside. This tridentate interaction of the ApA anion with the calcium coordination sphere probably enhances the stability of the observed ApA conformation. When combined with other crystallographic studies of ApA conformations, the crystal structure of this calcium salt provides additional evidence that dinucleoside phosphates have considerable conformational flexibility.

Adenosine Monophosphate↗

Early distant metastases from epithelioid sarcoma of the hand.

The authors describe a patient with epithelioid sarcoma in whom the presenting lesion was cervical lymph node metastasis. This proved to be a difficult diagnostic problem, until the occult primary tumor was discovered in the ipsilateral hand. A cerebral metastasis became evident early in the course of the disease. The authors believe this to be the first case reported in whom the presenting lesion was a nonregional metastasis. The rapid clinical progression of this patient's malignancy is of interest and illustrates the need for early intervention in patients with an epithelioid sarcoma, since the clinical course is not always indolent.

Adolescent↗

Crystallization and preliminary X-ray investigation of human erythrocytic purine nucleoside phosphorylase.

Crystals of human erythrocytic purine nucleoside phosphorylase have been grown from solutions of ammonium sulfate. The crystals are trigonal, space group R32; the hexagonal axes are a = 143.8(2) and c = 165.1(2) A. The crystals are moderately stable to x-rays and diffract beyond 3.0 A resolution. The experimental density of the crystals indicates that the molecular weight of the protein is 94,000. The three subunits are not related by crystallographic symmetry.

Crystallization↗

Crystallization and preliminary X-ray investigation of calmodulin.

Crystals of rat testis calmodulin, a multifunctional Ca2+-binding protein have been grown from solutions of 2-methyl-2,4-pentanediol. The crystals are triclinic, space group P1, with a = 29.79(4) A, b = 53.74(7) A, c = 24.78(3) A, alpha = 93.46(2)degrees, beta = 96.98(2)degrees, and gamma = 89.05(3)degrees. There is 1 calmodulin molecule per unit cell. The crystals are quite stable to x-rays and diffract beyond 2.5 A resolution.

Animals↗

Small-bowel stenosis after seat belt injury.

A case of small-bowel stenosis, which occurred one month after blunt abdominal trauma caused by a seat belt, is described. The literature concerning small-bowel injuries after blunt abdominal trauma is reviewed.

Adolescent↗

Large-capacity separation of malignant cells and lymphocytes from the Furth mast cell tumor in a reorienting zonal rotor.

The Furth murine mastocytoma was adapted to the ascitic form and separated into fractions enriched with respect to lymphocytes and malignant cells by velocity sedimentation in the SZ-14 reorienting zonal rotor or in the isokinetic gradient. Lymphocytes were more highly purified (p less than 0.01) in the isokinetic gradient than in the zonal rotor, i.e., lymphocytes comprised 99.1% of the nucleated cells in the purest fraction from the isokinetic gradient and 80.1% of the nucleated cells in the purest fraction from the zonal rotor. Neoplastic mast cells were similarly purified by the two methods; they comprised 67.7 and 78.5% of the nucleated cells in the purest fractions from the isokinetic gradient and zonal rotor, respectively. Up to 160 million tumor cells can be purified in a single step with the reorienting zonal rotor, whereas 30 to 40 million cells per gradient approach the limit of the isokinetic gradient. After centrifugation in the zonal rotor, recovery was 85.6 +/- 12% (S.D.) of the cells layered over the gradient; and the separated tumor cells retained their ability to form tumors when transplanted into mice. The separation of large numbers of lymphocytes and malignant cells from the same tumor in the SZ-14 rotor should aid in the biochemical and immunological characterization of cancer.

Animals↗

Calcium-carbohydrate bridges composed of uncharged sugars. Structure of a hydrated calcium bromide complex of alpha-fucose.

X-ray diffraction data were used to determine the crystal structure of a hydrated CaBr2 complex of alpha-fucose, a common terminal sugar of oligosaccharide chains on glycoproteins. Crystals of C6H12O5-CaBr2-3H2O are orthorhombic, space group P212121, with A equals 14.360(2), B equals 12.896(3), and C equals 8.043(1) A. Intensity data for 1442 independent reflections were measured with an automated diffractometer. A trial structure, obtained by the heavy-atom method, was refined by least-squares to R equals 0.052. Ca-2+ is chelated by a pair of hydroxyl groups from each of tow symmetry-related fucose molecules and is coordinated to three water molecules. Thus the structure consists of hydrated fucose-calcium-fucose bridges. The bridge geometry, which is dictated by the coordination requirements of Ca-2+, is like that of other calcium-carbohydrate complexes. Our results indicate that calcium-fucose interactions can provide an effective, sterospecific mechanism for cross-linking carbo hydrate chains. Similar calcium-carbohydrate bridges may be involved in a variety of Ca-2+-dependent agglutination and adhesion processes.

Binding Sites↗

Crystal structures of azathioprine dihydrate and 6-methylmercaptopurine trihydrate.

The crystal and molecular structures of 6-methylmercaptopurine trihydrate and of azathioprine dihydrate were determined by the use of three-dimensional, X-ray, diffractometer data and were refined by least squares. Both molecules crystallize in the N(9)-H tautomer form, in contrast to the N(7)-H tautomer form found in crystals of 6-mercaptopurine. Unlike 6-mercaptopurine, or other thiopurines that have unsubstituted thio groups, the sulfur atoms of 6-methylmercaptopurine and azathioprine do not act as hydrogen-bond acceptors in the crystal structures. These two derivatives of 6-mercaptopurine assume a conformation in which the substituents on the sulfur atom are directed away from the imidazole moiety of the purine.

Azathioprine↗

Three-dimensional structure of calmodulin.

The three-dimensional structure of calmodulin has been determined crystallographically at 3.0 A resolution. The molecule consists of two globular lobes connected by a long exposed alpha-helix. Each lobe binds two calcium ions through helix-loop-helix domains similar to those of other calcium-binding proteins. The long helix between the lobes may be involved in interactions of calmodulin with drugs and various proteins.

Allosteric Regulation↗

Solitary malignant peripheral nerve sheath tumor of the pancreas.

Primary malignant peripheral nerve sheath tumors of the pancreas are rare. This is a report of a 72 year-old African male who presented with an 8 lb. weight loss and anorexia. A computed tomography (CT) scan revealed a 12 cm mid pancreatic mass. An 85% pancreatectomy (with splenectomy) was performed. Immunohistopathologic and ultrastructural (electron microscopy) evaluation established the schwann cell origin of this neoplasm. The clinical management and pathologic findings are discussed in this report as well as a review of the literature.

Aged↗