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Biomedical subjects

D C Baker

Publications and source records attributed to D C Baker.

At least 91 records · Page 5Linked to original sources

Nicotinamide-adenine dinucleotide-methemoglobin reductase activity in erythrocytes from cats.

Reduced nicotinamide-adenine dinucleotide (NADH)-methemoglobin reductase activity in feline erythrocyte lysates was determined, using potassium ferricyanide as substrate. The optimum conditions for the assay were pH 8 and 37 C. Mean NADH-ferricyanide reductase activity in cats was 15.7 +/- 4.1 mumoles of substrate converted/g of hemoglobin/min. The migration of NADH-ferricyanide reductase was similar to that of the NADH-methemoglobin reductase (NADH diaphorase) on starch gel electrophoresis.

Animals↗

Evidence for the conversion of adenosine to 2'-deoxycoformycin by Streptomyces antibioticus.

The incorporation and distribution of 14C in 2'-deoxycoformycin, elaborated by Streptomyces antibioticus, were studied with [U-14C]glycine, [U-14C]adenosine and [U-14C]adenine. Similar ratios of 14C in the aglycon and carbohydrate portions of 2'-deoxycoformycin, ara-A, and adenosine isolated from the RNA indicated that [U-14C]adenosine was incorporated into 2'-deoxycoformycin without cleavage of the N-glycosylic bond. Following the addition of [U-14C]adenine, 98% of the 14C isolated from [14C]-2'-deoxycoformycin resided in the aglycon. 2'-Deoxycoformycin biosynthesis may not require the de novo purine biosynthetic pathway as evidenced by the failure to detect incorporation of [U-14C]glycine into 2'-deoxycoformycin. These data suggest that the biosynthesis of 2'-deoxycoformycin involves the incorporation of the carbon-nitrogen skeleton of an intact purine nucleoside or nucleotide, thereby implying that a purine ring is opened enzymatically between C-6 and N-1 and a one-carbon unit is added to form the 1,3-diazepine ring of 2'-deoxycoformycin.

Adenine↗

Synthesis and evaluation of a series of 2'-O-acyl derivatives of 9-beta-D-arabinofuranosyladenine as antiherpes agents.

A series of four 9-(2-O-acyl-beta-D-arabinofuranosyl)adenines (5a-d) was synthesized by acylation of 9-[3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-arabinofuranosyl]adenine (2), followed by removal of the tert-butyldimethylsilyl groups under conditions (HOAc, tetra-n-butylammonium fluoride) that prevented acyl migration. The four 2'-O-acyl derivatives 5a-d showed activity in vitro against herpes type 1 viruses [virus ratings = 1.5-2.6; MIC50 = 26-72 micrograms/mL (8.48-21.3 X 10(-5) M)]. The 2'-O-acetyl (5a) and 2'-O-valeryl (5d) derivatives were evaluated in a guinea pig model for genital herpes (herpes type 2); only 5a showed potent activity when given 6 or 24 h postinfection.

Animals↗

A three-step synthesis of (+/-)-beta-methyleneaspartic acid.

A simplified, three-step synthesis for (+/-)-beta- methyleneaspartic acid is described. Condensation of diethyl malonate with ethyl pyruvate gives 1,1,2- tricarbethoxyprop -1-ene, which is alpha-aminated with chloramine to give 1-amino-1,1,2- tricarbethoxyprop -2-ene. The latter is hydrolyzed in acid to give the title compound.

Aspartic Acid↗

Coping with the complexities of informed consent in dermatologic surgery.

Few medico-legal issues have generated as much controversy as informed consent--the right of patients to be fully informed about the risks, complications, and alternatives to a medical treatment or surgical procedure before deciding whether or not to submit to it. This paper discusses the complexities inherent in the legal doctrine of informed consent and their implications for dermatologic surgery. Particular emphasis is placed on the legal requirements for informed consent, as well as the problems associated with informing patients and their potential solutions.

Comprehension↗

Photoaffinity labeling of the indole sites on the Escherichia coli tryptophan synthase alpha-subunit.

The alpha subunit of the Escherichia coli tryptophan synthase catalyzes the reversible aldolytic reaction: Indole-3-glycerol phosphate in equilibrium indole + glyceraldehyde 3-phosphate. The use of 5-azidoindole as a photoaffinity label has made the generation of a number of enzyme-substrate complexes possible, each with a given degree of saturation of the two postulated indole sites. When assayed in the reverse reaction (indole-3-glycerol phosphate synthesis), samples of alpha subunit treated at concentrations of 5-azidoindole less than or equal to 2 mM show a progressive 30-40% activation. A gradual inactivation occurs only in samples irradiated at concentrations in excess of 2 mM 5-azidoindole, and this inactivation is complete at 8-10 mM. A quantitatively similar activation occurs in the forward reaction (indole synthesis), however inactivation in this case is incomplete, with complexes treated at 8-12 mM 5-azidoindole retaining 30-40% relative activity in this reaction. When treated alpha subunits were assayed for their abilities to complement the beta 2-subunit in the reactions indole + L-serine leads to L-tryptophan + H2O and indole-3-glycerol phosphate + L-serine leads to L-tryptophan + glyceraldehyde 3-phosphate, quantitatively lesser amounts of activation followed by total inactivation are observed over a similar range of 5-azidoindole concentrations.

Affinity Labels↗

An evaluation of certain chain-extended analogues of 9-beta-D-arabinofuranosyladenine for antiviral and cardiovascular activity.

Several nucleosides modified and chain extended at the 5'-position have been synthesized as follows: N6-benzamido- 9-(2,3-di-O-benzoyl-beta-D-arabino-pentodialdo-1,4-furanosyl)adenine, O=CHR, a leads to (E)-EtOCOCH=CHR (2) b leads to EtOCOCH2CH2R (3) c leads to H2NCOCH2CH2R (6) d leads to 1-(adenin-9- yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronamide (8); 3 e leads to ethyl 1-(adenin-9-yl)-1,5,6-trideoxy-beta-D-arabino-hepto-1, 4-furanuronate (5) f leads to 1-(adenin-9-yl)-1, 5,6-trideoxy-beta-D-arabino-hepto-1,4-furanuronic acid (4); 5 g leads to 9-(5,6-dideoxy-beta-D-arabino-hepto-1,4-furanosyl)adenine (7) [where a = EtOCOCH=PPh3; b = H2, Pd/C; c = Me2A1NH2; d = NH3/MeOH; e = NaOEt/EtOH; f = NaOH/MeOH; g = LiA1H4]. Both 7 and 8 show activity against herpes simplex virus type 1. The mechanism for such activity is unknown. Compounds 5 and 8 exhibited weak coronary vasodilation effects in dogs.

Adenosine Deaminase↗

Congenital infiltrating lipomatosis of the face: clinicopathologic evaluation and treatment.

Congenital lipomatosis of the face is characterized by collections of nonencapsulated, mature lipocytes which infiltrate local tissues and tend to recur after surgery. These lesions represent a distinct clinicopathologic entity that has not been previously reported in this location in children. Three children with congenital lipomatosis of the face were treated at the Institute of Reconstructive Plastic Surgery over a 2- to 14-year follow-up period. In each instance, pathologic evaluation by light and electron microscopy revealed similar lesions sharing the following morphologic criteria: (1) nonencapsulated tumors containing mature fat cells, (2) infiltration of adjacent muscle and soft tissue, (3) absence of malignant characteristics, (4) absence of lipoblasts, (5) presence of fibrous elements in conjunction with increased numbers of nerve bundles and vessels, and (6) hypertrophy of subjacent bone. All three lesions recurred after numerous excisions, some of which were extensive. All were benign by histologic examination and remained so for as long as 14 years. Surgical treatment improved the aesthetic appearance of each child despite evidence of tumor persistence. Although these tumors are benign, we recommend an early aggressive surgical approach to control the infiltrative nature of their growth and to improve facial appearance.

Child↗

Evaluation of prodrugs of 9-beta-D-arabinofuranosyladenine for therapeutic efficacy in the topical treatment of genital herpesvirus infections in guinea pigs.

Prodrugs of the antiviral agent 9-beta-D-arabinofuranosyladenine (araA), which were more effective than the parent compound in penetrating vaginal membranes in vitro, were synthesized and examined for efficacy in the topical treatment of genital infections with herpes simplex virus type 2 in female guinea pigs. Treatment with 10% araA-5'-monophosphate or 10% araA-5'-monovalerate twice a day for 7 days, starting 6 h after intravaginal inoculation with virus, completely aborted the primary infection. When initiation of treatment was delayed until 24 h postinfection, araA-5'-monophosphate and araA-5'-monovalerate were no longer effective in reducing the mean lesion scores or mean vaginal virus titers. Treatment with 5% acyclovir, starting at 24 h postinfection, failed to prevent genital lesion development but significantly reduced the peak mean lesion score (approximately 50%). Topical therapy with 10% araA-2',3'-diacetate, initiated at 24 h postinfection, was as effective as, if not more effective than, acyclovir in reducing the severity of herpes genitalis in guinea pigs. Treatment with 10% araA-2',3'-dipropionate or 10% araA-2',3'-dibutyrate was without benefit. Among a series of 5'-monoesters of araA, araA-5'-monobutyrate appeared to be the most effective but was less active than araA-2',3'-diacetate. These data indicate that araA-2',3'-diacetate may be an effective antiviral agent for topical use against genital herpesvirus infections.

Acyclovir↗

Hemoparasitism, humoral immunodeficiency, and an IgG1 fragment in a cow.

An adult cow with nonregenerative anemia was found to be infected with Eperythrozoon wenyoni and Trypanosoma theileri. Further laboratory testing revealed hypoalbuminemia, hypogammaglobulinemia, decreased numbers of circulating B lymphocytes, and presence of a serum immunoglobulin G1 fragment. Reduced B-lymphocyte regions in lymphoid tissue, evidence of chronic nephritis, and infection with Fasciola hepatica and Sarcocystis spp were found at necropsy. The cause of the acquired humoral immunodeficiency and the serum immunoglobulin G1 fragment was undetermined.

Anaplasmataceae Infections↗

Inhibitors of adenosine deaminase. Studies in combining high-affinity enzyme-binding structural units. erythro-1,6-Dihydro-6-(hydroxymethyl)-9-(2-hydroxy-3-nonyl)purine and erythro-9-(2-hydroxy-3-nonyl)purine.

erythro-1,6-Dihydro-6-(hydroxymethyl)-9-(2-hydroxy-3-nonyl)purine (4) was synthesized as a potential adenosine deaminase inhibitor, which combines in a single molecule two structural moieties, each of which possesses high affinity to a different region of the enzyme, the catalytic region and an auxiliary binding region which is specific for erythro-9-(2-hydroxy-3-nonyl)adenine (1). The potency of 4 (Ki = 1.2 x 10(-5) M) is about one-seventeenth that of erythro-9-(2-hydroxy-3-nonyl)purine (2; Ki = 6.8 x 10(-7) M), which contains only one high-affinity moiety. The mutually interfering rather than reinforcing effects of the two moieties may indicate that lack of simultaneous binding and thus provide insight into the relative geometry of the two binding regions of the enzyme.

Adenosine Deaminase Inhibitors↗

Paralysis of the mandibular branch of the facial nerve.

A direct and simple operation of transfer of the anterior belly of the digastric muscle with its attached tendon is presented. It was carried out in 36 patients, with three minor complications. It has proved effective in paralysis of the mandibular division of the facial nerve as a primary or secondary procedure. In ablative resections where this branch of the nerve is intentionally sacrificed, it is advised to do the muscle and tendon transfer as part of the primary operation. In aesthetic operations or where the status of the nerve (post-operatively) is not specifically know, it is advised to wait for spontaneous return for an interval of 3 to 6 months. If the improvement is not satisfactory, then this technique may be considered.

Facial Muscles↗