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G J White

Publications and source records attributed to G J White.

27 records · Page 2Linked to original sources

Solubilization and initial biochemical characterization of an IgE-destroying enzyme on rat peritoneal mast cells.

Previous studies had demonstrated that incubation of IgE with purified rat mast cells can result in the time and cell concentration-dependent destruction of the ability of the IgE to be bound to specific receptors on rat basophil leukemia cells. The IgE-destroying activity, which has an extremely acid pH optimum, resisted attempts at solubilization using detergents. However, it was solubilized in good yield by use of chaotropic salts and especially KOCN. The soluble activity is stable to freezing and thawing, and to heating to 68 degrees C for 60 min. It is promptly destroyed upon boiling. IgE destruction was linear with time up to 20 min and a series of products, mol. wts 138,000, 92,500, 60,000 and 36,500, are formed during the reaction. No pH optimum for the reaction could be found because, as the pH was lowered below 4.0, the spontaneous destruction of IgE became too great. At pH 4.75 the apparent Km for the reaction was 0.55 microM and Vmax was 0.4 nmoles IgE/10(4) mast cell equivalents/min. IgE-destroying activity could be inhibited by heat-inactivated serum, and by relatively high concentrations of crude alpha 1-antitrypsin, aprotinin, lima bean and soybean trypsin inhibitors and by p-nitroguanidinobenzoate. A large number of other protease inhibitors were inactive.

Animals↗

Inhibition of oxidative enzymes by anti-allergy drugs.

Lodoxamide tromethamine and several other anti-allergy drugs, i.e. inhibitors of rat passive cutaneous anaphylaxis, are inhibitors of purified xanthine oxidase. Inhibition is noncompetitive with Ki's in the 1-13 micromolar range. Lodoxamide tromethamine had no effect on another flavoprotein, glucose oxidase. Other studies have shown several of these drugs are inhibitors of aldose reductase. It is speculated that the anti-allergy drugs inhibit mediator release from mast cells by blocking univalent electron transfers which are essential for release.

Aldehyde Reductase↗

Development of new antiallergic drugs (cromolyn sodium, lodoxamide tromethamine). What is the role of cholinergic stimulation in the biphasic dose response?

The antiallergy drugs, cromolyn sodium and lodoxamide tromethamine (U-42,585E) show in vitro dose responses which are bell-shaped or biphasic in mast cells. The nature of the biphasic dose response is poorly understood; however, through the use of specific antagonists, it has been possible to show that at the high concentrations of these drugs leading to enhanced histamine release or multiple high-dose tachyphylaxis, a cholinergic receptor is stimulated in the cell. This receptor is muscarinic in nature and can be blocked by atropine or quinuclidinyl benzilate (QNB). Prevention of multiple dose tachyphylaxis to either drug can be modulated by pretreatment with atropine or QNB. High concentrations of both drugs cause the cell accumulation of cyclic-guanosine monophosphate through stimulation of guanyl cyclase and prevention of cGMP breakdown by inhibition of the phosphodiesterase (PDE) for cGMP.

Animals↗

PCR-based detection of bacterial DNA after antimicrobial treatment is indicative of persistent, viable bacteria in the chinchilla model of otitis media.

PURPOSE: Bacterial deoxyribonucleic acid (DNA) has been previously detected by polymerase chain reactions (PCR) in a significant percentage of culturally-sterile pediatric middle-ear effusions. The current study was designed to determine whether this represents the existence of viable bacteria or the persistence of residual DNA in the middle-ear cleft. MATERIALS AND METHODS: The middle-ear cavities of two sets of chinchillas were inoculated with either: 1) 100 colony-forming units (CFU) of live Haemophilus influenzae, 2.2 x 10(6) CFU of pasteurized Moraxella catarrhalis, and 1000 ng of DNA (>10(8) genomic equivalents) from Streptococcus pneumoniae; or 2) 100 CFU of live S pneumoniae, 2.2 x 10(6) CFU of pasteurized M catarrhalis and 1000 ng of purified DNA from H influenzae. Animals were treated with ampicillin for 5 days beginning on day 3. A single-point longitudinal study design was used for sampling to eliminate the possibility of contamination. RESULTS: No DNA was detectable from the heat-killed bacteria or the purified DNA after day 3. However, DNA from the live bacteria persisted through day 21, even though all specimens were culture-negative following the initiation of antimicrobial therapy. CONCLUSION: These findings indicate that purified DNA and DNA from intact but nonviable bacteria do not persist in the middle-ear cleft in the presence of an effusion, even following high copy inoculation. In contrast, antibiotic-treated bacteria persist in some viable state for weeks as evidenced by the differential ability of the PCR-based assay systems to detect the live bacteria, but not detect the heat-killed organisms.

Ampicillin↗

Bacteriologic aspects of epidural analgesia.

The incidence of contamination of catheters and syringes used during epidural analgesia for parturients and the effectiveness of bacterial filters were investigated. The effect of bupivacaine on bacterial viability and growth was also studied. Syringes in 5/101 cases were contaminated, while catheter tips located in the epidural space were sterile. Organisms isolated were skin commensals and probably originated on the hands of anesthetic personnel. Bupivacaine (0.25%) was bacteriocidal to S epidermidis and Corynebacterium spp at 37C but not at room temperature. These findings illustrate the efficacy of using bacterial filters during continuous epidural analgesia. New syringes should be used for each epidural injection as insurance against seeding of bacteria in the presence of a defective filter.

Anesthesia, Epidural↗