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Biomedical subjects

G Christie

Publications and source records attributed to G Christie.

At least 55 records · Page 3Linked to original sources
PubMed1988

Drug-protein conjugates--XVII. The effect of storage on the antigenicity and immunogenicity of benzylpenicillin in the rat.

The disposition and immunogenicity of freshly prepared and stored solutions of benzylpenicillin (BP) and benzylpenicillenic acid (BPE), a degradation product of BP, were studied. No IgG anti-benzylpenicilloyl (BPO) antibodies were detected by enzyme-linked immunosorbent assay (ELISA) following daily i.p. or i.m. administration to male Wistar rats of BP (2.7 mmol/kg) freshly dissolved in 0.5% glucose, for 4 consecutive days at 4-week intervals. In contrast, IgG anti-BPO antibodies were detected following both chronic i.p. and i.m. administration of BP (2.7 mmol/kg) stored for 24 hr at room temperature in 0.5% glucose. An IgG anti-BPO response was obtained only after the high dose, following daily i.m. administration of BPE (27 mumol/kg, 2.7 mumol/kg, 0.24 mumol/kg). The specificity of the IgG antibody for the BPO-determinant was confirmed by ELISA inhibition with BPO-amino-caproate. Circulating BPO plasma-protein antigens were detected by a modified ELISA following i.p. and i.m. administration of both stored and fresh BP. Significantly lower BPO-antigen levels were detected in serum following BPE administration. Irreversible binding of BP to 75% rat plasma proteins was of the same magnitude when freshly dissolved in phosphate buffer or in 0.5% glucose (2.63 +/- 0.32% and 2.55 +/- 0.25% bound, respectively after 3 hr incubation at 37 degrees). Irreversible binding was significantly greater (P less than 0.05) when the BP was stored prior to incubation with the protein (3.81 +/- 0.27%). The major degradation product of stored BP was benzylpenicilloic acid; a small amount of BPE (0.2% of incubated BP) was detected in stored but not fresh BP. Thus, the increased immunogenicity of BP stored for 24 hr at room temperature may be due to the formation of reactive degradation products such as BPE in vitro, which can then form immunogenic drug-protein conjugates in vivo. These experiments also show that although BP and BPE form drug-protein conjugates in vivo, circulating levels of antigen do not relate to the immunogenicity of either of the compounds.

Animals↗
PubMed1988

Propofol for induction of anaesthesia in children. A comparison with thiopentone and halothane inhalational induction.

The induction characteristics, dosage requirements, cardiovascular and respiratory effects of propofol with added lignocaine were compared with those of thiopentone and halothane inhalational induction in two groups of children aged 1-5 years and 5-10 years. Propofol induction produced significantly greater decreases in blood pressure, particularly in the 1-5 year age group. Heart rate was maintained well with all three induction techniques. Pain on injection into a vein on the dorsum of the hand was significantly more common with propofol despite the addition of lignocaine. However, this was mild in the majority of children and did not interfere with the induction of anaesthesia. The incidence of respiratory depression and other adverse effects was low with all three induction methods. The mean induction doses of both intravenous agents were greater in the 1-5-year age group. The ratio of thiopentone to propofol dose was approximately 2.5:1 in both age groups. The high incidence of pain on injection with propofol may prove to be a significant drawback to its otherwise satisfactory use in children.

Anesthesia, Inhalation↗
PubMed1988

A survey of the prevalence of penicillin-specific IgG, IgM and IgE antibodies detected by ELISA and defined by hapten inhibition, in patients with suspected penicillin allergy and in healthy volunteers.

1. IgG, IgM and IgE anti-benzylpenicilloyl (BPO) antibody activities were determined by enzyme-linked immunosorbent assay (ELISA) in sera from 100 patients who claimed to be allergic to penicillin, and from 50 healthy volunteers. Continuous frequency distributions for all three classes of anti-BPO antibody, defined as differential binding (delta OD) to BPO-human serum albumin (HSA) and HSA, were obtained for both groups. 2. For IgM and IgE classes the anti-BPO activities were slightly but statistically significantly higher in the patient group compared with the volunteer group. 3. Hapten inhibition ELISAs were performed to confirm specificity for the BPO determinant. On the basis of antibody activities (delta OD values) greater than or equal to 0.3 and 50% inhibition of binding in the presence of 100 micrograms ml-1 BPO-caproate, BPO-specific IgG antibody was identified in 4/100 of the patients' sera and in 1/50 of the volunteers' sera; BPO-specific IgM was identified in 7/100 patients' sera and 1/50 volunteers' sera; and BPO-specific IgE in 5/100 patients' sera and 1/50 volunteers' sera. 4. Not all sera with differential antibody binding to BPO-HSA/HSA were inhibited by the BPO hapten. Hence, hapten inhibition assays are essential for the unambiguous demonstration of drug specific antibodies.

Adult↗
PubMed1987

Drug-protein conjugates--XIII. The disposition of the benzylpenicilloyl hapten conjugated to albumin.

The disposition and metabolic fate of benzylpenicillin conjugated to a protein, human serum albumin (HSA), were compared with those of free penicillin in the rat. The conjugate was prepared by in vitro incubation of [3H]-benzylpenicillin and HSA at pH 10.8 for 24 hr at 37 degrees, conditions which favour the formation of penicilloyl-lysine residues. The synthetic conjugate was cleared more slowly from plasma than free penicillin after intravenous administration; thus at 3 hr, concentrations of 5.08 +/- 0.50% dose/ml of the conjugate (0.31 microCi; 2.92 mg protein) was obtained. In an earlier study a concentration of 0.03 +/- 0.01% dose/ml was obtained after administration of free BP (2.7 mmol kg-1). During this time, 1.41 +/- 0.50% of the conjugate dose was excreted in urine while 5.0 +/- 0.2% of the dose was excreted in bile. Tissue analysis indicated that the liver contained 15.3 +/- 0.9% of the dose, while other tissues contained less than 6% of the dose. In long term metabolism studies it was found that 39.5 +/- 1.0% and 46.5 +/- 0.9% of the dose (0.43 microCi; 6.33 mg protein) was excreted in the urine after 3 and 7 days respectively. The principal metabolite (63-68%) excreted in both bile and urine was identified on the basis of cochromatography and fast atom bombardment mass spectrometry as benzylpenicilloic acid, indicating that the conjugate undergoes specific cleavage at the bond between the benzylpenicilloyl moiety and the protein. In vitro degradation studies indicate that the metabolism occurs primarily in the liver. Therefore benzylpenicilloic acid excreted in urine, after administration of free BP, may be formed either by direct hydrolysis of the beta-lactam ring, and/or result from catabolism of protein conjugates formed in vivo.

Animals↗
PubMed1987

Drug-protein conjugates--XII. A study of the disposition, irreversible binding and immunogenicity of penicillin in the rat.

The disposition, irreversible binding and immunogenicity of benzylpenicillin (BP) were studied in male Wistar rats. [3H]BP, administered i.v. to anaesthetized rats at two doses (27 mumol/kg, 2.7 mmol/kg), showed dose-dependent kinetics: plasma and tissue concentrations of total BP were disproportionately increased at the higher dose. BP was rapidly cleared from the plasma at both doses (less than 0.05% of administered dose/ml plasma after 3 hr). In spite of the disproportionately elevated levels of total BP after the higher dose, covalent binding to plasma proteins was quantitatively similar as a percentage of the dose at both doses. Three hours after i.v. injection of 27 mumol/kg and 2.7 mmol/kg of the drug, 5.6% +/- 1.7% and 3.3% +/- 1.1% respectively of circulating BP was covalently bound, representing less than 0.004% of the administered dose bound per ml of plasma in each case. Covalent binding of BP to rat plasma proteins in vitro was of a similar magnitude to that observed in vivo: 1.6% +/- 0.4% of BP was bound to 25% rat plasma after 3 hr incubation at 37 degrees. In a separate series of experiments the immunogenicity of BP was studied by chronic administration of the drug to rats. Following daily i.v. or i.m. administration of BP (27 mumol/kg, 270 mumol/kg, 2.7 mmol/kg) for 4 consecutive days at 4-week intervals (three series of injections) neither IgG nor IgM anti-benzylpenicilloyl (BPO) antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the high dose of BP was discontinued after the first series of injections due to local necrosis. In contrast to free BP, BPO-keyhole limpet haemocyanin (BPO-KLH, 42 nmol BP bound/mg KLH) administered by single i.v. injection at 4-week intervals at two doses (20 and 200 micrograms conjugate/kg, corresponding to 0.84 and 8.4 nmol BPO/kg) readily induced IgG and IgM anti-BPO antibody responses (median IgG titres were 872 and 5470 one week after the third injection of the low and high dose of conjugate respectively; corresponding IgM titres were 4513 and 22,866). The specificity of the IgG and IgM antibodies for the BPO determinant was confirmed by ELISA inhibition with BPO-aminocaproate. These experiments show that BP binds irreversibly, but to a limited extent, to plasma proteins in vivo, and that such a degree of conjugation appears to be insufficient to elicit a detectable anti-BPO antibody response.

Animals↗
PubMed1982

The prevention of hepatitis B with vaccine. Report of the centers for disease control multi-center efficacy trial among homosexual men.

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

Adult↗
PubMed1978

Haematological and blood chemistry "comparison values" for clinical pathology in poultry.

Twelve blood chemistry values, six haematological values and bodyweight were estimated for six-week-old specific-pathogen-free brown leghorns. Observations were based on 208 birds sampled from 11 groups. Subsequently the same values were estimated for specific pathogen free brown leghorns and broiler hybrids of differing ages. These estimates have been designated "comparison values" and were intended for reference use in clinical pathology. Results were compared with 14 "comparison value" estimated obtained previously for six-week-old commercial broiler hybrids. Haematological values varied with age and type of bird. Differences were observed between bird types in serum protein, serum cholesterol, uric acid, calcium and potassium levels and in weight. The significance of these differences is discussed.

Age Factors↗
PubMed1977

Effect of transportation on blood metabolites in broilers.

1. Groups of 30 broilers from seven flocks were bled and weighed at the farm and a further sample of 10 broilers from each flock was transported from 8 to 16 km to the laboratory prior to bleeding and weighing. 2. One haematological and 11 biochemical analyses were made on each blood sample. 3. Although transportation did lead to significant differences in certain variables, the trends were consistent and sampling following transit is considered acceptable for clinical pathology studies.

Animals↗
PubMed1975

Melanoma cells resistant to inhibition of growth by melanocyte stimulating hormone.

Melanocyte stimulating hormone (MSH) enhances melanization but inhibits proliferation of Cloudman S91 melanoma cells in culture. We have isolated variants of these cells that can grow in the presence of MSH. The conclusions we have reached from analyses of these cells are the following: (1) Basal tyrosinase activity (monophenol monooxygenase; monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1), i.e., the activity that is present in the absence of added MSH, is related through a common biochemical pathway to MSH-mediated control of growth. (2) MSH-inducible tyrosinase activity does not appear to be related to MSH control of growth. (3) The morphological changes that occur following the addition of MSH or cAMP are related to controls of growth and not to those of melanization.

Animals↗