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Biomedical subjects

C D Anderson

Publications and source records attributed to C D Anderson.

At least 55 records · Page 3Linked to original sources

Studies of the 2':3'-cyclic nucleotide phosphodiesterase of Haemophilus influenzae.

The 2':3'-cyclic nucleotide phosphodiesterase:3'-nucleotidase of Haemophilus influenzae was purified from a periplasmic preparation by affinity chromatographic techniques. The enzyme-catalysed hydrolysis of 2':3'-cyclic AMP to adenosine without accumulation of the intermediate substrate 3'-AMP was demonstrated by high performance liquid chromatography. Competitive inhibition of the enzyme by a variety of nucleosides and mononucleotides indicated the presence of either purine or pyrimidine bases to be essential for selective interactions with the enzyme, and confirmed the need for a 3'-position phosphate for the functioning of mononucleotides as substrates for the enzyme. The enzyme had a molecular weight of 79 000, was stable at low temperatures and was thermally denatured at temperatures above 50 degrees C.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Cytostatic agents and contact allergy: the efferent limb.

The effects upon the contact allergic reaction in the guinea pig of the 3 cytostatic agents most commonly used for their immunosuppressant properties, cyclophosphamide, methotrexate and azothioprine, have been investigated in an experimental model which allows comparison of the qualitative and quantitative aspects of the dermal inflammatory infiltrate and the macroscopic response. The 3 agents were given in single, relatively high doses and had effects on the dermal inflammatory infiltrate which varied in nature, degree and time course. Changes often showed a cyclical development with time, with "rebound" often following initial changes. Although cyclophosphamide had the most marked effect, all agents affected the mononuclear, basophil and eosinophil dermal infiltrates at some point in the experiment. Cyclophosphamide was the only agent found to affect the total white cell count of peripheral blood, but the leukopenia did not affect recruitment of mononuclear cells to the dermis. In the period immediately after administration of cyclophosphamide and methotrexate, the macroscopic score increased. Whilst the mechanism of this effect is unclear, it may be a manifestation of a basophil, perhaps IgE mediated reaction. Further manipulation of dose and dose interval may result in administration schedules relevant to the treatment of cell-mediated hypersensitivity in clinical practice.

Animals↗

UVA photosensitivity in photosensitive bullous disease of chronic renal failure.

3 chronic renal failure patients with bullous skin disease are reported. Only 1 was on maintenance hemodialysis, but all were on frusemide. Porphyrin studies failed to show classical porphyric disease. The 3 patients tested showed low minimal etyrhema doses (MED) to ultraviolet A (UVA) but normal threshold to ultraviolet B (UVB).

Adult↗

Properties and applications of immobilized snake venom NAD glycohydrolase.

The NAD glycohydrolase (NADase) from Bungarus fasciatus snake venom was adsorbed on concanavalin A-Sepharose, and demonstrated to retain both hydrolase and transglycosidase activities in the bound form. The matrix-bound enzyme was stable to repeated washing with buffer and storage at 4 degrees C. The bound enzyme exhibited the same Km value for hydrolysis of nicotinamide-1,N6-ethenoadenine dinucleotide as previously measured with the soluble, purified form of the enzyme. The bound NADase was used repeatedly for a preparative-scale synthesis of 3-acetylpyridine adenine dinucleotide. It was further demonstrated that the immobilized enzyme could be prepared directly from crude snake venom, thus avoiding the time required for purification. The application of the immobilized snake venom NADase for the preparation of pyridine nucleotide coenzyme analogs has many advantages over procedures used previously for analog synthesis.

Catalysis↗

The influence on the dermal cellular infiltrate of topical steroid applications and vehicles in guinea pig skin: normal skin, allergic and toxic reactions.

The mechanisms of the anti-inflammatory effects of corticosteroids are uncertain but could be explained by an influence on infiltrating leukocytes. Our method for the qualitative and quantitative investigation of the dermal cellular infiltrate makes it possible to study the effects of topically applied corticosteroid preparations and vehicles on the infiltrating leukocytes of normal skin, allergic and toxic reactions in guinea pig skin. Ointment and cream vehicles as well as corticosteroid cream and ointment preparations often caused erythema and increased mononuclear infiltrate after only short periods of application (24-72 h). The strongest steroid ointment gave the most marked macroscopic response and propylene glycol preparations the most marked cellular response. In both toxic and allergic reactions, application of steroid preparations after the provocation gave no beneficial result either macroscopically or microscopically. Macroscopic scores were worsened by cream and ointment preparations. Although steroid solutions had no beneficial effect, they caused no detrimental effect. The guinea pig seems to be extremely sensitive to irritants and has not proved to be a suitable model for this approach to the study of the efficacy of topically applied steroids.

Administration, Topical↗

3-aminopyridine 1,N6-ethenoadenine dinucleotide phosphate: a fluorescent reagent for NADP-requiring enzymes.

3-Aminopyridine 1,N6-ethenoadenine dinucleotide phosphate (epsilon-AADP) was synthesized from 3-aminopyridine adenine dinucleotide phosphate by reaction with chloroacetaldehyde. The reaction was monitored by high-pressure liquid chromatography. The product, epsilon-AADP, was purified by ion-exchange chromatography followed by a Sephadex G-10 desalting process. Spectrophotometric and fluorimetric properties of epsilon-AADP were obtained at neutral pH. Diazotization of epsilon-AADP was documented by azodye formation at pH values below 3 and the diazotized derivative was shown to react rapidly with sulfhydryl compounds at neutrality. As an analog of NADP, epsilon-AADP was demonstrated to be an effective NADP-competitive inhibitor of NADP-requiring dehydrogenases, reductases, and an NAD glycohydrolase.

Adenine Nucleotides↗

A test of delayed recovery following stressful stimulation in four psychosomatic disorders.

Sternbach proposed a three component model to account for the emergence of psychosomatic symptoms. He hypothesized that if an individual exhibited (1) marked response stereotypy, and (2) inadequate homeostatic restraints, then (3) exposure to activating situations would result in psychosomatic episodes. The main purpose of the present study was to examine the second component of the Sternbach model, homeostatic inadequacy, as indicated by impaired rate of recovery from stressful stimulation. In addition, the presence of response stereotypy was investigated in this study. Ten subjects from each of 5 diagnostic groups (rheumatoid arthritis, essential hypertension, migraine headache, tension headache, and healthy controls) were observed under conditions of unstructured relaxation, easement (exposure to stimuli intended to enhance relaxation), mild stress, and recovery from stress. Forearm and forehead muscle potential, peripheral temperature, electrodermal response, heart rate and systolic and diastolic blood pressure were monitored during these sessions. Although evidence of symptom specific response stereotypy was regularly observed, slowness of recovery did not emerge as a robust phenomenon in the four psychosomatic disorders investigated. The phenomenon was consistently observed in the arthritic subjects, absent in hypertensives and tension headache subjects, and ambiguous for migraine subjects.

Arousal↗

The chemical modification of papain with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.

The reaction of the water-soluble carbodimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), with active papain in the presence of the nucleophile ethyl glycinate results in an irreversible inactivation of the enzyme. This inactivation is accompanied by the derivatization of the catalytically essential thiol group of the enzyme (Cys-25) and by the modification of 6 out of 14 of papain's carboxyl groups and up to 9 out of 19 of the enyzme's tyrosyl residues. No apparent irreversible modification of histidine residues is observed. Mercuripapain is also irreversibly inactivated by EDC/ethyl glycinate, again with the concomitant modification of 6 carboxyl groups, up to 10 tyrosyl residues, and no histidine residues; but in this case there is no thiol derivatization. Treatment of either modified native papain or modified mercuripapain with hydroxylamine results in the complete regeneration of free tyrosyl residues but does not restore any activity. The competitive inhibitor benzamidoacetonitrile substantially protects native papain against inactivation and against the derivatization of the essential thiol group as well as 2 of the 6 otherwise accessible carboxyl groups. The inhibitor has no effect upon tyrosyl modification. These findings are discussed in the context of a possible catalytic role for a carboxyl group in the active site of papain.

Amino Acids↗