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Biomedical subjects

G Taylor

Publications and source records attributed to G Taylor.

At least 343 records · Page 19Linked to original sources
PubMed1985

Immune responses to mycoplasma infections of the respiratory tract.

Mycoplasmas are capable of causing respiratory disease in a number of species of animals. The pathogenicity of the mycoplasma species ranges from those that cause major disease outbreaks and economic loss to what might be considered the more highly evolved and successful parasites at the other end of the spectrum that survive for long periods in the host without being recognised and evicted. This prolonged colonisation of mucous membranes which is typical of many mycoplasmas is related to certain unique features of the mycoplasma and its interaction with the hosts immune system. An initial step in infection is the attachment of the mycoplasma to the epithelial lining of the respiratory tract. Lack of cell wall confers plasticity and may engender the intimate association of mycoplasma and host cell that has been noted. This in turn may favour persistence of the extracellular parasite. Before the specific immune response is produced avoidance of the non-specific immune mechanisms would clearly aid survival. Both passive (capsules) and active (toxic effects) mechanisms of avoiding phagocytosis have been proposed. Both humoral and cell mediated responses are generated by mycoplasma infections. The serum antibody response follows the usual course IgM, G and A. The indications of cell mediated immunity that have been reported include; delayed type hypersensitivity reactions, lymphocyte transformation responses and inhibition of macrophage migration. The concept that the pathological lesions are in a large part due to host reactivity is well accepted. The lung lesions may contain infiltrating and dividing lymphocytes some of which are producing specific antibody. Evidence for the lung lesion in some animals being partly due to the hosts cell mediated response has also been produced. The local immune response appears to be of greater relevance to immunity to infection than the systemic response, in general the association between local antibody and immunity is much better than for serum antibody. Of particular note is the high contribution of local IgG production, particularly in the lower respiratory tract. Attempts are now being made to use this increased understanding to produce effective killed vaccines that produce immune responses in the lung. Such studies will hopefully lead to the development of 'killed' vaccines that are effective. It can be urged that mycoplasmas would be less pathogenic if they did not produce an inflammatory response and some species have been shown to have an immunosuppressive effect. Such a property could affect the lesion, and hence pathogenicity, and also aid mycoplasma persistence.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Megalourethra.

We present 5 examples of megalourethra. All 5 cases were associated with the spectrum of the triad syndrome, ranging from minor hydronephrosis and undescended testis to gross hydronephrosis incompatible with survival. Initial management of this urethral defect is drainage followed later by reconstruction.

Child, Preschool↗
PubMed1985

Immunologic evaluation in the nutritional assessment of children with cancer.

Eighty-one newly diagnosed untreated pediatric cancer patients (48 hematopoeitic malignancies, 17 solid tumors, 16 benign diseases) were evaluated with immunologic and nutritional parameters. The mean absolute lymphocyte count was adequate in the three groups. Reduced T-lymphocytes were seen in the solid tumors. Mitogenic response of hematopoietic and solid tumor patients' lymphocytes was low. Correlation of immunologic, dietary, and nutritional factors showed that for patients with solid tumors there was a positive significant correlation between weight/height percent and lymphocyte reactivity to phytohemagglutinin, concanavalin A, and pokeweed mitogen (p less than .05). Iron intake showed a significant positive correlation with in vitro mitogen reactivity for the solid tumor group (p less than .05) and benign diseases (p less than 0.01). Immune derangements found among patients with hematopoietic malignancies can be due to replacement of normal bone marrow with malignant cells. In solid tumor patients mitogen reactivity appears to be a reflection of nutritional state, and dietary iron is a possible factor.

Adolescent↗
PubMed1985

Cytotoxic lymphocytes in the lungs of mice infected with respiratory syncytial virus.

Mice infected with respiratory syncytial virus (RSV) developed cytotoxic lymphocytes in the lungs, which lysed RSV-infected, but not uninfected cells. Cytotoxic activity was greatest 7 to 9 days after infection, was virus-specific, MHC-restricted and abolished by treatment of lymphocytes with anti-Thy 1.2 or with anti-Lyt 2.2 sera and complement. There was a close temporal relationship between the appearance of these cytotoxic lymphocytes in the lung and clearance of virus. In contrast, RSV persisted in the lungs of athymic (nude) mice and such animals failed to develop RSV-specific cytotoxic lymphocytes. Thus, cytotoxic T-cells may have an important role in recovery from RSV infection.

Animals↗
PubMed1985

Comparison of venous and capillary blood sampling for the clinical determination of tobramycin serum concentrations.

Tobramycin concentrations have been determined in serum from capillary, venous and arterial blood samples taken from 16 patients during and after surgery. In 73 paired samples the concentrations in capillary samples were not significantly different from those measured in venous samples. The small concentration differences were neither dependent upon sampling time nor core-peripheral temperature differences. In 26 paired samples, concentrations in capillary samples were not significantly different from those determined in arterial samples. We conclude that concentrations in capillary samples are precise and unbiased estimators of venous concentrations and may be used in the adjustment of tobramycin dosage regimens.

Adult↗
PubMed1985

Changes in the disposition of promethazine during multiple dosing in the rabbit.

During a multiple dosing regimen, the area under the promethazine blood concentration-time profile progressively decreased indicating auto-induction of metabolism. The increase in promethazine clearance (mean 35%) was not reflected in changes in either elimination half-life or minimum blood concentrations during the dosing interval. This was attributed to a deep compartment in the disposition of promethazine in the rabbit. The changes in promethazine clearance were accompanied by proportionally larger changes in the clearance of the monodesmethylpromethazine metabolite. The effect of promethazine pretreatment on the clearance of antipyrine was also studied and was found to be significantly increased by a mean of 17% following pretreatment with promethazine. However, the changes in the clearance of antipyrine did not highly correlate with those of promethazine and monodesmethylpromethazine. This may indicate that promethazine induces metabolic systems in the rabbit for which antipyrine is not a good substrate.

Animals↗
PubMed1985

Strain differences in susceptibility to murine respiratory mycoplasmosis in C57BL/6 and C3H/HeN mice.

Not only is murine respiratory mycoplasmosis, due to Mycoplasma pulmonis, a complication of biomedical research, it provides excellent animal models to study the development of a naturally occurring respiratory disease induced by an infectious agent. The understanding of pathogenic mechanisms of disease can be greatly facilitated by studying genetic differences in susceptibility. Five strains of mice with various H-2K haplotypes were examined for their susceptibility to murine respiratory mycoplasmosis; of these, C57BL/6 and C3H/HeN mice were chosen for additional study. There were no significant differences in the incidence of infection in either the upper or lower respiratory tract or in the severity of upper respiratory tract lesions in the two strains as determined at 14 days postinfection. In striking contrast, the C57BL/6 mice were significantly more resistant to the development of gross and microscopic lung lesions and to death due to pneumonia as shown by an almost 100-fold difference in the 50% lethal dose, 50% gross pneumonia dose, and 50% microscopic lesion dose. The most apparent differences in lung lesions between the two strains were in the severity of acute lesions of the bronchial epithelium, the amount of mixed inflammatory response in the alveoli, and the amount of lymphoid infiltrates. All were significantly more severe in C3H/HeN mice. In addition, more C3H/HeN mice developed antibody responses to M. pulmonis. The amount of antibody correlated with lesion severity in both strains.

Animals↗
PubMed1985

Effect of promethazine and isosafrole on rat-hepatic microsomal mono-oxygenase activity: comparison with classic inducers phenobarbitone and beta-naphthoflavone.

The characteristics of induction of rat-hepatic microsomal mono-oxygenase activity by promethazine and isosafrole have been investigated and compared with the classic inducers phenobarbitone and beta-naphthoflavone. Both promethazine and isosafrole pretreatments result in increased cytochromes P-450, and enhanced NADPH-cytochrome c reductase, aminopyrine N-demethylase, dichloronitroanisole O-demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activity. Isosafrole but not promethazine increased the liver to body weight ratio. It is concluded that promethazine and isosafrole pretreatment produces an induction of the rat-hepatic microsomal mono-oxygenase system which shows both phenobarbitone- and polycyclic aromatic hydrocarbon-type characteristics.

Animals↗
PubMed1985

Direct analysis of differentiation proteins in normal and leukemic human granulocytes by high-performance liquid chromatography.

The feasibility of the use of reverse-phase high-performance liquid chromatography (RP-HPLC) for detecting differences in the protein phenotypes of highly purified fractions of normal and chronic myelogenous leukemic (CML) mature granulocytes isolated from peripheral blood was determined. At least 21 protein peaks were consistently and reproducibly detected in the RP-HPLC profiles of acetonitrile-trifluoroacetic acid extracts of normal granulocytes. This assay takes only 60 minutes to perform and can be done on 4 X 10(6) granulocytes (approximately the number of granulocytes in 1 ml normal blood). Furthermore, sodium dodecyl sulfate-gel electrophoresis of the RP-HPLC fractions provides a second dimension to the analysis of the polypeptide pattern of these cell lysates. Analyses of subcellular fractions by these methods revealed that most of the major peaks in the RP-HPLC profiles of intact granulocytes originate mainly from the granule and membrane fractions. Although the protein phenotypes of mature granulocytes were remarkably uniform among normal individuals, those of mature granulocytes obtained from the blood of CML patients were consistently abnormal and varied considerably among individual patients. The results indicate that the approach used here could have useful application in the study of abnormal granulocyte differentiation in leukemia.

Acetonitriles↗
PubMed1984

Noncholinesterase actions of an irreversible acetylcholinesterase inhibitor on synaptic transmission and membrane properties in autonomic ganglia.

Superfusion of the organophosphorous acetylcholinesterase inhibitor soman (pinacolyl methylphosphonofluoridate; 0.01-25 microM) produced a dose-dependent reduction of extracellularly and intracellularly recorded synaptic responses in the isolated rat superior cervical ganglia at frequencies of orthodromic stimulation that do not normally produce synaptic depression. The magnitude of depression was dependent upon the frequency of stimulation (0.02-1 Hz), was maintained after the removal of soman from the superfusion solution, and recovered by over 65% during periods of inactivity. The depression of synaptic transmission produced by soman was not dependent upon the inhibition of acetylcholinesterase (AChE) activity by this agent. Transmission was increasingly depressed by doses of soman greater than those needed to inactivate all measurable ganglionic AChE activity. Dose-dependent depression of synaptic transmission in soman also occurred after pretreatment with the irreversible AChE inhibitor diisopropylphosphofluoridate (DFP; 100 microM), which inhibited greater than 98% of the AChE activity in the ganglia. Soman produced a decline in the input resistance, resting potential, spike amplitude, and spike threshold and a reduction in the hyperpolarizing afterpotential. Soman-induced depression of synaptic transmission was not due primarily to a blockade of postsynaptic nicotinic receptors. At concentrations of soman which produced significant depression in transmission, ganglionic depolarization produced by bath-applied carbamylcholine (carbachol) was either slightly depressed or facilitated. In the presence of soman, repetitive focal application of acetylcholine or carbachol did not reveal use-dependent desensitization. Muscarinic antagonists, atropine and pirenzepine, protected against the use-dependent depression of synaptic transmission induced by soman. These results suggest that a principal site of action for soman is at the presynaptic terminal and that this site is sensitive to muscarinic receptor blockade.

Animals↗
PubMed1984

A comparison of three vaccines against respiratory syncytial virus in calves.

An inactivated vaccine against respiratory syncytial virus (RSV) was compared with two live vaccines. The inactivated (GC) vaccine consisted of glutaraldehyde-fixed bovine nasal mucosa cells persistently infected with RSV and emulsified with oil adjuvant. The live vaccines were a modified virus (MV) derived from a bovine strain of RSV and a temperature-sensitive mutant (ts-1) derived from a human strain. The GC vaccine was inoculated subcutaneously into 12 calves and the live vaccines intramuscularly into eight calves each. Nine unvaccinated calves acted as controls. The vaccines were administered in two doses 3 weeks apart and all calves were challenged intranasally with 2 X 10(7) p.f.u. of bovine RSV 3 weeks after the second dose. At the time of challenge calves given GC, MV and ts-1 vaccines had mean serum neutralizing antibody titres of 25, 19 and 2 respectively; mean titres of IgG1 antibody by radioimmunoassay were log10 4.5, 1.3 and 2.6 respectively and mean zone areas by single radial haemolysis (SRH) were 107, 27 and 36 mm2 respectively. Eleven of 12 calves given GC vaccine were completely protected against challenge but all control animals and those given the two live vaccines were infected. The mean peak titre of virus in nasal swabs of control calves was 3.0 log10 p.f.u./ml and the mean duration of virus shedding was 6.8 days. Both these parameters were significantly reduced in animals given MV and ts-1 vaccines: mean peak titres were 2.1 and 2.4 log10 p.f.u./ml and mean duration of shedding was 3.4 and 3.3 days respectively. Thus, protection correlated better with RSV antibody detected by radioimmunoassay and SRH than with neutralizing antibody. These results are discussed in relation to the possible mechanism by which protection was mediated.

Animals↗
PubMed1984

Drug metabolite concentration-time profiles: influence of route of drug administration.

In order to assess the contribution of an active metabolite to the overall pharmacological response following drug administration it is necessary to characterise the metabolite concentration-time profile. The influence of route of drug administration on metabolite kinetics has been investigated by computer simulation. Comparisons between simulated profiles and published concentration-time data have been carried out. A route dependence in metabolite concentration-time curves is readily apparent provided the metabolite kinetics are formation rate limited and the hepatic clearance of drug is greater than 25 l/h (medium to highly cleared). Oral drug administration produces a triphasic metabolite concentration-time profile whereas only two phases are discernable after intravenous drug administration. The magnitude of the difference in maximum metabolite concentration is directly proportional to the hepatic clearance of drug due to first-pass metabolite production. The route dependence in the shape of the metabolite concentration-time curves is most dramatic when the absorption and distribution of drug and the elimination of metabolite is rapid. A reduction in the rate of either of these processes alters the shape of the metabolite concentration-time profile such that the consequence of first-pass metabolite formation may be reduced.

Administration, Oral↗
PubMed1984

Respiratory syncytial virus infection in mice.

The A2 strain of human respiratory syncytial virus replicated in the nose and lung of BALB/c mice, with virus growing to higher titers in older animals than in younger animals. Virus was recovered from the nose between days 2 and 7 with peak titers on days 3 and 4, and from the lungs between days 2 and 9, with peak titers on days 4 through 6. Serum antibody developed 2 weeks after infection. Viral antigen was demonstrated in the alveolar cells of the lung by immunofluorescence. Histopathological changes included infiltration by mononuclear cells of the peribronchiolar and perivascular tissue, some interstitial thickening, and formation of multinucleated giant cells. Virus could not be recovered from the respiratory tract of mice inoculated with bovine strains of respiratory syncytial virus. Growth of the A2 strain of human respiratory syncytial virus in different cell lines affected its infectivity for mice. Infection of BALB/c mice with respiratory syncytial virus provides a highly reproducible model for the study of the pathogenesis of and mechanisms of immunity to this virus.

Age Factors↗
PubMed1984

The effect of pertussis vaccine on the insulin-dependent diabetes induced by streptozotocin in mice.

Protective effect of pertussis vaccine (PV) against the development of insulin-dependent diabetes (IDD) induced by streptozotocin (STZ) in young CD-1 male mice were studied. When PV at a dose of 1.2 X 10(10) microorganism was administered on -10, 0, or +4 d relative to a single injection of STZ (60 mg/kg body wt) on d 0, it completely aborted the development of IDD after 140 d. When PV was given on +30 d after STZ injection and followed by PV booster injections, 66% of mice reverted to normoglycemic state. Intact islet cells in the pancreas were confirmed by histologic findings and normal plasma insulin values. The effect of PV was compared with that of boiled PV in another model of IDD induced by multiple injections of STZ (40 mg/kg for five doses). In this model, 60% of mice either remained or reverted to normoglycemic state with PV and booster injections whereas boiled PV protected 40% of mice from developing IDD. The protective effect appeared to reside in the biologic property of both pertussigen and endotoxin of Bordetella pertussis.

Animals↗
PubMed1984

The characterization and uses of monoclonal antibodies to respiratory syncytial virus.

Fifteen hybridomas secreting monoclonal antibodies against respiratory syncytial virus (RSV) have been produced. Three react with nucleoprotein (MW 42 000 daltons), 1 with phosphoprotein (MW 36 000 daltons), 1 with a larger protein (MW 60 000 daltons) and 10 with the fusion glycoprotein (MW 46 000 + 22 000 daltons). By immunofluorescent staining of infected cells, 5 monoclonal antibodies bind to cytoplasmic inclusions and the remainder give diffuse cytoplasmic fluorescence. Virus infectivity is neutralized by two monoclonal antibodies. Thirteen react with both bovine and human strains of RSV, two fail to react with three human strains. The antibodies have been used to induce passive protection in mice against challenge with RSV and to purify viral components on immunoadsorbent columns.

Animals↗
PubMed1984

Monoclonal antibodies protect against respiratory syncytial virus infection in mice.

Twenty-five monoclonal antibodies (Mab) to respiratory syncytial virus (RSV) and two to hepatitis B virus were inoculated intravenously into mice. Twenty-four hours later the mice were challenged intranasally with RSV. Eleven of 14 Mab against fusion protein and four out of six Mab against a larger glycoprotein (GP84) significantly reduced the titre of RSV in the lungs when mice were killed 5 days later. Five Mab against three other RSV proteins and two Mab against hepatitis B virus had no significant effect on RSV infection. These results indicated that serum IgG against one epitope on the fusion protein and another on the larger glycoprotein (GP84) will completely protect mice against challenge. These epitopes are primary candidates for an RSV vaccine produced by techniques of gene cloning and peptide synthesis.

Animals↗