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David E Anderson

Publications and source records attributed to David E Anderson.

41 records · Page 3Linked to original sources
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Endowing RNase H-inactive antisense with catalytic activity: 2-5A-morphants.

A convergent synthetic approach was used to conjugate 2',5'-oligoadenylate (2-5A, p5'A2' [p5'A2'](n)()p5'A) to phosphorodiamidate morpholino oligomers (morphants). To provide requisite quantities of 2-5A starting material, commercially and readily available synthons for solid-phase synthesis were adapted for larger scale solution synthesis. Thus, the tetranucleotide 5'-phosphoryladenylyl(2'-->5')adenylyl(2'-->5')adenylyl(2'-->5')adenosine (p5'A2'p5'A2'](2)p5'A2', tetramer 2-5A, 9) was synthesized starting with 2',3'-O-dibenzoyl-N(6),N(6)-dibenzoyl adenosine prepared from commercially available 5'-O-(4-monomethoxytrityl) adenosine. Coupling with N(6)-benzoyl-5'-O-(4,4'-dimethoxytrityl)-3'-O-(tert-butyldimethylsilyl) adenosine-2'-(N,N-diisopropyl-2-cyanoethyl)phosphoramidite, followed by oxidization and deprotection, generated 5'-deprotected dimer 2-5A. Similar procedures lengthened the chain to form protected tetramer 2-5 A. The title product 9 p5'A(2'p5'A)(3) (tetramer 2-5A) was obtained through phosphorylation of the terminal 5'-hydroxy of the protected tetramer and removal of remaining protecting groups using concentrated ammonium hydroxide-ethanol (3:1, v/v) at 55 degrees C and tetrabutylammonium fluoride (TBAF) in THF at room temperature, respectively. The 2-5A-phosphorodiamidate morpholino antisense chimera 11 (2-5A-morphant) was synthesized by covalently linking an aminolinker-functionalized phosphorodiamidate morpholino oligomer with periodate oxidized 2-5A tetramer (p5'A2'[p5'A2'](2)p5'A). The resulting Schiff base was reduced with cyanoborohydride thereby transforming the ribose of the 2'-terminal nucleotide of 2-5A N-substituted morpholine. RNase L assays demonstrated that this novel 2-5A-antisense chimera had significant biological activity, thereby providing another potential tool for RNA ablation.

Antineoplastic Agents↗
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Evaluation of a sheep laparoscopic uterine trauma model and repeat laparoscopy for evaluation of adhesion formation and prevention with sodium carboxymethylcellulose.

OBJECTIVE: To evaluate topical application of 1% sodium carboxymethyl cellulose (SCMC) for prevention of postoperative adhesions in a laparoscopic model of uterine trauma in sheep. STUDY DESIGN: Experimental study. ANIMALS: Fourteen non-pregnant ewes. METHODS: Ewes were randomly assigned to 1 of 2 groups: control (saline solution) or 1% SCMC treatment. By left flank laparoscopy, traumatic forceps were used to create serosal trauma (1.5 x 5 cm) and hemorrhage on the left uterine horn. Either 30 mL saline solution or 30 mL 1% SCMC was applied topically to the traumatized uterine horn. Adhesion formation was evaluated by repeat laparoscopy at days 14 and 21. Sheep were euthanatized on day 28 for necropsy evaluation of adhesions. RESULTS: Five control sheep had adhesions of the uterine horn by day 14, but only 4 had adhesions at day 21, and 2 at day 28. Adhesions did not occur in SCMC-treated sheep. No adhesions occurred elsewhere in the abdomen. CONCLUSIONS: Laparoscopically created uterine trauma is an effective method for induction of uterine adhesions, and laparoscopy is an excellent method for serial evaluation of adhesion formation. SCMC (1%) was effective at preventing adhesion formation in sheep and no inflammatory response was noted. CLINICAL RELEVANCE: SCMC (1%) should be considered for prevention of adhesions in abdominal surgery in sheep.

Animals↗
PubMedDate not supplied

(99M)Tc-ciprofloxacin in imaging of clinical infections in camelids and a goat.

(99M)Tc-ciprofloxacin was used to image five adult camelids and a juvenile goat with clinical and/or radiographic signs of infection. (99m)Tc-ciprofloxacin (range 10-33 MBq/kg) was injected intravenously and a series of 2-min static images were acquired at 1- and 4-h postinjection. At 24-h postinjection, 5-min static images were acquired. Only the skull or abdomen was imaged in the adults; the whole body was imaged in the goat. The quality of the 1-, 4-, and 24-h studies was evaluated subjectively. Normal and abnormal areas of (99m)Tc-ciprofloxacin uptake were recorded and subjectively graded as mild, moderate or intense. Image quality was best 4-h postinjection. Twenty-four-hour images were poor because of insufficient radioactivity. (99m)Tc-ciprofloxacin imaging resulted in true positive or true negative scans in four of six animals. Two false-negative studies occurred. Intense (99m)Tc-cirofloxacin activity was seen in the lungs and urinary bladder, moderate/intense activity in the kidneys, and mild activity in the physes/epiphyses, liver and intermittently in the gastrointestinal tract. The normal distribution of (99m)Tc-ciprofloxacin in camelids/small ruminants differed from people. Further studies to determine the sensitivity and specificity of infection detection using (99m)Tc-ciprofloxacin in animals are warranted.

Animals↗