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Biomedical subjects

D C Baker

Publications and source records attributed to D C Baker.

At least 73 records · Page 4Linked to original sources
PubMed1988

Anemia of inflammation in dogs infected with Ehrlichia platys.

Ten adult male dogs were inoculated with Ehrlichia platys, and blood samples were collected throughout the infection to evaluate the hematologic changes with respect to serum biochemical analytes. All dogs developed a mild, normocytic, normochromic anemia by postinoculation day 7, with significantly (P less than 0.05) decreased serum iron concentration and total iron-binding capacity. Stainable bone marrow iron appeared normal or increased throughout the infection. By postinoculation day 31, the PCV was not significantly different from the pretreatment value. All dogs became hypergammaglobulinemic, leukopenic, hypoalbuminemic, and hypocalcemic during the infection. These findings were compatible with the syndrome of anemia of inflammation.

Anemia↗
PubMed1987

Biosynthesis of 2'-deoxycoformycin: evidence for ring expansion of the adenine moiety of adenosine to a tetrahydroimidazo[4,5-d][1,3]diazepine system.

2'-Deoxycoformycin (2'-dCF), a nucleoside antitumor agent produced in trace quantities by Streptomyces antibioticus, has been shown in earlier work to originate from the intact carbon-nitrogen framework of adenosine. Additional experiments using 13C and two-dimensional Fourier transform NMR techniques, together with radiolabeling studies, identify the C-1 of D-ribose, and not the tetrahydrofolate "C-1 pool", as the source of the C-7 carbon in the aglycon of 2'-dCF. These results show that the adenine portion of adenosine (or a nucleotide thereof) undergoes a unique ring expansion, by insertion of a -CH2- unit between the N-1 and C-6 of the adenine ring, to furnish the 1,3-diazepine portion of 2'-dCF.

Adenosine↗
PubMed1987

Hydride transfer stereospecificity of rat liver aldehyde dehydrogenases.

The stereospecificity of hydride transfer to NAD+ by several forms of rat liver aldehyde dehydrogenase was determined by a nuclear magnetic resonance method. The forms included several mitochondrial and microsomal isozymes from normal liver, as well as isozymes from xenobiotic-treated and tumor cells. The proton added to NAD+ comes exclusively from the aldehyde substrate and in all cases was A (pro-R)-stereospecific.

Aldehyde Dehydrogenase↗
PubMed1987

Cells of origin of the branches of the facial nerve: a retrograde HRP study in the rabbit.

The origin of different branches of the facial nerve in the rabbit was determined by using retrograde transport of HRP. Either the proximal stump of specific nerves was exposed to HRP after transection, or an injection of the tracer was made into particular muscles innervated by a branch of the facial nerve. A clear somatotopic pattern was observed. Those branches which innervate the rostral facial musculature arise from cells located in the lateral and intermediate portions of the nuclear complex. Orbital musculature is supplied by neurons in the dorsal portion of the complex, with the more rostral orbital muscles receiving input from more laterally located cells while the caudal orbital region receives innervation from more medial regions of the dorsal facial nucleus. The rostral portion of the ear also receives innervation from cells located in the dorsomedial part of the nucleus, but the caudal aspect of the ear is supplied exclusively by cells located in medial regions. The cervical platysma, the platysma of the lower jaw, and the deep muscles (i.e., digastric and stylohyoid) receive input from cells topographically arranged in the middle and ventral portions of the nuclear complex. It is proposed that the topographic relationship between the facial nucleus and branches of the facial nerve reflects the embryological derivation of the facial muscles. Those muscles that develop from the embryonic sphincter colli profundus layer are innervated by lateral and dorsomedial portions of the nuclear complex. The muscles derived from the embryonic platysma layer, including the deep musculature, receive their input from mid to ventral regions of the nuclear complex.

Animals↗
PubMed1987

Coagulation defects of aflatoxin intoxicated rabbits.

Twelve New Zealand white rabbits were intoxicated with aflatoxin B1. Most rabbits developed a coagulation defect near the time of death. Immediately prior to death there were significant decreases in factors V, VII, and VIII coagulant activities and fibrinogen concentration without a change in plasma fibrin(ogen) degradation product concentration, platelet number, and detectable plasma fibrin monomers. Microscopic evidence of disseminated intravascular coagulation was present in one rabbit with marked, diffuse hepatic necrosis. Terminal serum albumin concentration was significantly correlated to plasma factors V and VII activities and fibrinogen concentration. The coagulation defect of aflatoxicosis is primarily due to diminished hepatic synthesis of coagulation factors except when hepatic necrosis is severe enough to initiate intravascular coagulation and consumption of coagulation factors.

Aflatoxin B1↗
PubMed1987

Acute Ehrlichia platys infection in the dog.

Ten dogs were inoculated with Ehrlichia platys (E. platys) from an acutely infected dog. Two dogs were necropsied on each of days 7, 14, 21, 28, and 35 post-inoculation, and tissues were collected and either fixed in formalin or frozen for light microscopic examination of lesions or E. platys antigen localization in tissues. Serum antibody titers to E. platys and serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities were also determined. The significant light microscopic findings were lymph node follicular hyperplasia and crescent-shaped hemorrhages in the splenic periarteriolar lymphoid sheaths beginning day 7 post-inoculation. There was significant megakaryocyte hyperplasia of bone marrow on days 28 and 35 post-inoculation. Ehrlichia platys antigen was in macrophages at 14 days post-inoculation which corresponded to the initial decline in platelet numbers. Initial thrombocytopenia and splenic crescent-shaped hemorrhages were temporally related, however the degree of lesion development and prominence were not related to subsequent platelet numbers.

Acute Disease↗
PubMed1986

Transition-state stabilization by adenosine deaminase: structural studies of its inhibitory complex with deoxycoformycin.

Experiments with radioactive deoxycoformycin indicate that the inhibitor is released from calf intestinal adenosine deaminase after the enzyme-inhibitor complex is disrupted by denaturation. Experiments with 2H2O and H218O indicate that the enzyme does not catalyze elimination-addition reactions that could have led to reversible covalent derivatization of the enzyme. Ultraviolet difference spectra and the influence of pH on inhibitor binding indicate that deoxycoformycin is bound intact as the neutral species, at a binding site that is less polar than solvent water. The enzyme-inhibitor complex appears to be held together by hydrogen bonds of extraordinary stability (ca. 10 kcal/mol). These results suggest that deamination proceeds by direct water attack, the enzyme acting as a general-base catalyst.

Adenosine Deaminase Inhibitors↗
PubMed1986

Hemosiderin in leukocytes of dogs with immune-mediated hemolytic anemia.

Hemosiderin granules were identified in blood neutrophils and monocytes of three dogs. The brownish granules were 1 to 4 microns in diameter and stained positively for iron with Prussian blue stain. All three dogs had evidence of immune-mediated hemolytic anemia and received whole blood transfusions prior to observation of hemosiderin. The mechanism of hemosiderin accumulation by blood leukocytes from these dogs was undetermined. Iron overload produced by administration of whole blood transfusions during immune-mediated hemolytic anemia was implicated as a causative factor.

Journal Article↗
PubMed1985

Spontaneous epimerization of (S)-deoxycoformycin and interaction of (R)-deoxycoformycin, (S)-deoxycoformycin, and 8-ketodeoxycoformycin with adenosine deaminase.

(R)-Deoxycoformycin (pentostatin), (S)-deoxycoformycin, and 8-ketodeoxycoformycin were compared as inhibitors of calf intestine adenosine deaminase. In contrast to (R)-deoxycoformycin, which had been demonstrated as a tight-binding inhibitor with a dissociation constant of 2.5 X 10(-12) M [Agarwal, R. P., Spector, T., & Parks, R. E., Jr. (1977) Biochem. Pharmacol. 26, 359-367], (S)-deoxycoformycin and 8-ketodeoxycoformycin are slope-linear competitive inhibitors with respect to adenosine. The kinetic constants are 33 microM for inhibition by (S)-deoxycoformycin, 43 microM for 8-ketodeoxycoformycin, and 16 microM for the Km for adenosine. The stereochemistry of carbon 8 of the diazepine ring therefore causes a (1.3 X 10(7]-fold change in the affinity for the enzyme which is specific for the R configuration. This difference is attributed to an induced conformational change which cannot be initiated by the S isomer or the 8-keto analogue of (R)-deoxycoformycin. The studies were complicated by the need to remove traces of tight-binding inhibitor(s) from (S)-deoxycoformycin, since as little as 0.001% of the R isomer causes significant inhibition. The R and S isomers of deoxycoformycin are unstable in neutral or mildly acidic aqueous solutions. Isomerization of the secondary hydroxyl at carbon 8 of the diazepine ring is one of the reactions, resulting in S to R and R to S conversions for deoxycoformycins. Opening of the aglycon is also a major reaction. The tight-binding inhibitor generated from (S)-deoxycoformycin was identified as (R)-deoxycoformycin by high-pressure liquid chromatography, spectroscopy, circular dichroism, and chemical criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1985

Lyme disease. A cause of bilateral facial paralysis.

Recently we had the opportunity of treating a boy from the northeastern region of the United States in whom bilateral facial palsies developed. After obtaining a detailed history and performing a thorough physical examination, the findings suggested Lyme disease. We herein discuss our evaluation and treatment of this child as well as review the otolaryngologic manifestations of this rare disease.

Anti-Bacterial Agents↗
PubMed1985

Hydrolysis and solvent-dependent 2'----5'and 3'----5' acyl migration in prodrugs of 9-beta-D-arabinofuranosyladenine.

As a prerequisite to quantitative in vivo studies to further explore the promising topical activity of the 2',3'-di-O-acetyl derivative of 9-beta-D-arabinofuranosyladenine (ara-A) against herpes virus infections, the kinetics of solution degradation of the 2',3'-di-O-acetyl derivative and the 2'-,3'-, and 5'-monoacetates were investigated. The rates of aqueous solution hydrolysis were found to be consistent with rank order predictions based on a consideration of substituent effects. Preliminary in vivo hydrolysis data, however, do not correlate with such predictions, indicating a need for more systemic studies of the effect of molecular structure on enzyme-catalyzed hydrolysis. An important reaction of the 2'-3'-diester and the 3'-monoester in aqueous solution, in addition to ester hydrolysis, is 3'----5' acyl migration. 2'----5' Acyl migration does not occur in water but is the predominant migration pathway in organic solvents, as verified by studies in acetonitrile. 1H NMR spectroscopy was employed to study the dependence of the conformation of the sugar ring on the solvent environment. Although a change in the equilibrium between the C(2')endo and C(3')endo conformational states does occur, it is not a dramatic change and cannot explain the solvent selectivity observed in the acyl migration kinetics.

Chemical Phenomena↗
PubMed1985

Influence of 1-dodecylazacycloheptan-2-one (Azone) on the topical therapy of cutaneous herpes simplex virus type 1 infection in hairless mice with 2',3'-di-O-acetyl-9-beta-D-arabinofuranosyladenine and 5'-O-valeryl-9-beta-D-arabinofuranosyladenine.

The predictive value of a recently developed physical model was tested in the topical treatment of cutaneous infections caused by herpes simplex virus type 1 in hairless mice with two ester prodrugs of 9-beta-D-arabinofuranosyladenine (ara-A) (1). The tests were conducted with 2',3'-di-O-acetyl-ara-A (4) and 5'-O-valeryl-ara-A (3) topically applied with and without 15% 1-dodecylazacycloheptan-2-one (2) (Azone), a percutaneous penetration enhancer. In addition to the in vivo studies, in vitro diffusion cell experiments with excised, full-thickness skin from hairless mice were conducted to determine the penetration enhancement effects of 2. As previously observed, 2 was able to induce remarkably large (100- to 1000-fold) flux enhancements in these in vitro experiments. Consistent with predictions based on the physical model studies, formulations of 3 and 4 without 2 had little or no influence on the pathogenesis of the herpes simplex virus type 1 infections; when 2 was present in the formulations, both 3 and 4 had dramatic therapeutic effects consistent with the predictions made with the physical model. Prodrug 4 with 2 was especially efficacious in the prevention of virus-induced lesions and in the survival of all animals. Similar results were obtained with acyclovir plus 2 in this model system.

Acyclovir↗