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Biomedical subjects

C R Bird

Publications and source records attributed to C R Bird.

At least 37 records · Page 2Linked to original sources

Carotid artery stenosis: clinical efficacy of two-dimensional time-of-flight MR angiography.

To assess the clinical efficacy of two-dimensional time-of-flight magnetic resonance (MR) angiography in the evaluation of carotid artery stenosis, a group of patients was evaluated in which 73 vessels were studied with both MR and conventional angiography. Four experienced neuroradiologists each scored both the MR and conventional angiograms in a blinded manner by using a standardized scoring scheme. Comparison of the scores revealed a high degree of correlation. In particular, MR angiography served to discriminate reliably between mildly narrowed and severely narrowed or occluded vessels. Furthermore, severe stenoses were accurately discriminated from occlusions in all cases. MR angiography is a robust and accurate modality for the characterization of carotid artery stenosis. It is useful in conjunction with routine MR imaging of the brain in the evaluation of the patient with suspected carotid arterial disease.

Carotid Arteries↗

Nature of the endogenous pyrogen (EP) induced by influenza viruses: lack of correlation between EP levels and content of the known pyrogenic cytokines, interleukin 1, interleukin 6 and tumour necrosis factor.

Fever in influenza results from the release of endogenous pyrogen (EP) following virus-phagocyte interaction and its level correlates with the differing virulence of virus strains. However, the different levels of fever produced in ferrets by intracardial inoculation of EP obtained from the interaction of different virus strains with ferret of human phagocytes did not correlate with the levels of interleukin 1 (IL-1), IL-6 or tumour necrosis factor in the same samples as assayed by conventional in vitro methods. Hence, the EP produced by influenza virus appears to be different to these cytokines.

Animals↗

Production of polyclonal and monoclonal antibodies to human granulocyte colony-stimulating factor (GCSF) and development of immunoassays.

Murine monoclonal antibodies and a sheep polyclonal antiserum against recombinant human granulocyte colony-stimulating factor (GCSF) have been produced. These have been used to develop an immunoassay which can detect 250 pg/ml (25 U) of both natural and recombinant human GCSF. The assay involves forming a complex between GCSF and a monoclonal anti-GCSF, binding of the complex to microtitre wells coated with sheep anti-GCSF and detection of the bound complex with 125I-labelled sheep anti-mouse IgG. Unlike the classical bone marrow assay and other cell line based bioassays for GCSF, the immunoassay was specific for the cytokine, showing no cross-reactivity with GM-CSF, IL-6, IL-3 or IL-1 alpha and -beta. The assay does not exhibit interfering matrix effects when used for the estimation of human GCSF in serum.

Animals↗

Inheritance and effect on ripening of antisense polygalacturonase genes in transgenic tomatoes.

The role of the cell wall hydrolase polygalacturonase (PG) during fruit ripening was investigated using novel mutant tomato lines in which expression of the PG gene has been down regulated by antisense RNA. Tomato plants were transformed with chimaeric genes designed to express anti-PG RNA constitutively. Thirteen transformed lines were obtained of which five were analysed in detail. All contained a single PG antisense gene, the expression of which led to a reduction in PG enzyme activity in ripe fruit to between 5% and 50% that of normal. One line, GR16, showed a reduction to 10% of normal PG activity. The reduction in activity segregated with the PG antisense gene in selfed progeny of GR16. Plants homozygous for the antisense gene showed a reduction of PG enzyme expression of greater than 99%. The PG antisense gene was inherited stably through two generations. In tomato fruit with a residual 1% PG enzyme activity pectin depolymerisation was inhibited, indicating that PG is involved in pectin degradation in vivo. Other ripening parameters, such as ethylene production, lycopene accumulation, polyuronide solubilisation, and invertase activity, together with pectinesterase activity were not affected by the expression of the antisense gene.

Food Technology↗

Expression of a truncated tomato polygalacturonase gene inhibits expression of the endogenous gene in transgenic plants.

Tomato plants were transformed with a chimaeric polygalacturonase (PG) gene, designed to produce a truncated PG transcript constitutively. In these plants expression of the endogenous PG gene was inhibited during ripening, resulting in a substantial reduction in PG mRNA and enzyme accumulation. This inhibition was comparable to that achieved previously using antisense genes. The expression of the truncated gene in ripe fruit was substantially lower than its expression in green fruit. Thus expression of both the endogenous and truncated genes is reduced in ripe fruit in which both are active. The implication of this observation is discussed in relation to the possible mechanism whereby sense constructs inhibit gene expression.

Blotting, Northern↗

Cytokines in skin lesions of psoriasis.

Cytokine levels were compared in aqueous extracts of stratum corneum from psoriatic lesions and normal heel. Samples from heel contained high levels of interleukin-1 alpha (IL-1 alpha) and beta measured in immunoassays, although only the IL-1 alpha was biologically active. No other cytokines could be detected in heel samples. Interleukin-1 (IL-1) levels were dramatically reduced in lesional samples. A neutrophil chemoattractant was found in all lesional extracts, and was demonstrated to be mainly interleukin-8 (IL-8) using a specific neutralizing antiserum. Tumor necrosis factor alpha (TNF-alpha) and beta (TNF-beta), and interferon alpha (IFN-alpha) and gamma (IFN-gamma) were detected in lesional extracts using immunoassays, however, no equivalent biological activities could be detected. Interleukins 2 (IL-2), 4 (IL-4), and 6 (IL-6), granulocyte and granulocyte/macrophage colony stimulating factor (GM-CSF), could not be detected in any samples. IL-8 is therefore the only biologically active cytokine shown in this study to be elevated in psoriatic lesional extracts, and may therefore play a role in the pathogenesis of the disease.

Chemotaxis, Leukocyte↗

Gliomas: classification with MR imaging.

The findings at magnetic resonance (MR) imaging in a group of 36 pathologically verified supratentorial gliomas were analyzed and compared with the biopsy diagnoses (a) to determine whether MR imaging could be used to classify astrocytic-series tumors into a three-tiered system of low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme; and (b) to evaluate MR imaging features that may aid in this classification. The MR characteristics evaluated were crossing of the midline, edema, tumor signal heterogeneity, hemorrhage, border definition, cyst formation or necrosis, and mass effect. The statistically significant MR characteristics (positive predictors) were mass effect (P = .0000) and cyst formation or necrosis (P = .0512). The MR accuracy rate approached that of neuropathologic diagnosis, which is subject to sampling errors. MR imaging may serve as an adjunct in case management when the clinical course and MR findings appear to be at odds with the neuropathologic diagnosis.

Anaplasia↗

Demonstration of cytokines in biological medicines produced in mammalian cell lines.

Commercially produced biological medicines may contain cytokines secreted by mammalian cell lines. Several such cell lines were found to produce interleukin 6 and, after stimulation, to secrete interleukin 1, tumour necrosis factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. High levels of interleukin 6 were detected in several vaccines and rDNA-derived proteins, and certain vaccines contained interleukin 1, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Some preparations of human monoclonal antibodies were also found to contain interleukin 1 and tumour necrosis factor. Cytokines may contribute to certain types of adverse reactions to these products.

Animals↗

Control and manipulation of gene expression during tomato fruit ripening.

Ripening is a complex developmental process involving changes in the biochemistry, physiology and gene expression of the fruit. It is an active process characterised by changes in all cellular compartments. cDNA cloning has been used as an approach to analyse changes in gene expression during fruit ripening. This has revealed that several genes are switched on specifically during fruit ripening, including one encoding polygalacturonase (PG), a major cell wall protein. These cDNA clones have been used to study the expression of the genes in normal and ripening mutant fruits, and under environmental stress conditions. The PG gene has been isolated and it has been demonstrated that 1450 bases 5' of the coding region are sufficient for the tissue- and development-specific expression of a bacterial marker gene in transgenic tomatoes. Antisense RNA techniques have been developed to generate novel mutant tomatoes in which the biochemical function of this enzyme and its involvement in fruit softening has been tested.

Cloning, Molecular↗

Presence of the inflammatory cytokines IL-1, TNF, and IL-6 in preparations of monoclonal antibodies.

We have detected significant levels of IL-1, TNF and IL-6 in ascitic fluid from mice injected with different hybridomas. Each of these murine cytokines is active on a wide range of both human and murine target cells, and all are involved in inflammatory responses in vivo. We could not detect TNF or IL-1 in culture supernatant from the hybridoma line, used to generate the ascites; however, one out of ten did produce high levels of IL-6. These cytokines can interfere in many in vitro systems where monoclonal antibodies are used as diluted ascitic fluid to inhibit their ligands. A potentially more serious problem could arise with monoclonal antibodies used for therapy, in vivo diagnosis, or as ex vivo reagents. The use of monoclonal antibodies derived from culture supernatants is, therefore, obviously preferable to use of ascitic fluid for clinical applications, however, even with supernatant it cannot be assumed that cytokines are not present. Cytokine levels should, therefore, be monitored in all starting solutions and if present, their clearance during purification should be determined.

Animals↗

Human cellular immune responses to Bordetella pertussis infection.

We have compared the responses of peripheral blood leucocytes from three groups (i) patients suffering from pertussis (whooping cough), (ii) clinical staff caring for those patients and laboratory staff working with Bordetella pertussis, and (iii) staff with no known recent contact with B. pertussis. In vitro stimulation with filamentous haemagglutinin (FHA) caused significant increases in proliferation of only the patient group's lymphocytes. In vitro stimulation with pertussis toxin (PT) caused a large increase in proliferation of lymphocytes from all three groups and in the patient group the increase in proliferation was related to the dose of PT. Interleukin 2 (IL-2) production by leucocytes from all three groups was significantly increased following challenge with FHA or PT. The increases in IL-2 production were greatest in lymphocytes from patients with pertussis. Challenge with toxoided pertussis toxin had no effect on either proliferation or IL-2 production in any of the groups.

Adolescent↗

Subtle encephalomyelitis in children: a variant of acute disseminated encephalomyelitis.

Four children with chronic, mild, nonspecific symptoms are described in whom magnetic resonance imaging (MRI) showed the presence of multifocal white-matter lesions suggestive of acute disseminated encephalomyelitis. The children ranged in age from 14 months to 15 years. The clinical picture was vague and inconclusive and consisted of several months of headaches, irritability, clumsiness, and personality change. Physical examinations were noncontributory. Laboratory investigation revealed no other cause of the demyelination. All of the patients have done well without any treatment, with a disappearance of symptomatology. The white-matter lesions on MRI scan in these children may indicate subtle exposure to a myelinolytic antigen. It has been suggested that such an exposure may create a state of complete or partial resistance to the encephalitogenic potential of the next infection or immunization. With complete resistance, the patient remains healthy and with partial resistance progressive demyelination results. Verification of these findings by others would suggest a possible benefit of a multicenter study of such patients, with virological, HLA testing, and long-term follow-up, in understanding the etiopathogenesis of multiple sclerosis.

Acute Disease↗

Unenhanced and gadolinium-DTPA-enhanced MR imaging in postoperative evaluation in pediatric brain tumors.

Gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) is a chelated paramagnetic contrast agent under clinical trial for use in magnetic resonance (MR) imaging. The increased signal intensity following the intravenous infusion of contrast medium may improve the ability of MR imaging to delineate tumors. The use of this method in 15 pediatric patients with suspected brain-tumor recurrence was analyzed. All 15 patients underwent postoperative Gd-DTPA-enhanced MR imaging, and residual tumor was demonstrated in nine of them. Based on the findings of the enhanced MR studies, four patients had additional surgery, two underwent radiation therapy, and one was given immunotherapy. Continued surveillance was recommended for the remaining eight patients. In all cases the enhanced MR imaging studies were superior to the unenhanced studies in regard to the qualitative and quantitative assessment of the residual tumor. Gadolinium-DTPA-enhanced MR imaging appears to be a safe and effective means of providing an accurate postoperative assessment of residual disease in pediatric brain-tumor patients. It is as effective as contrast-enhanced computerized tomography and has the sensitivity and anatomic resolution provided by MR imaging. The most useful role of this agent was in the postoperative period, in assessing the adequacy of surgical resection. This technique is recommended as the procedure of choice in the postoperative assessment and long-term surveillance of patients with brain tumors.

Adolescent↗

Neutrophil chemoattractant and IL-1-like activity in samples from psoriatic skin lesions. Further characterization.

The IL-1-like neutrophil chemoattractant activity previously reported by us to be present in the stratum corneum of psoriatic skin lesions has now been characterized further. Aqueous extracts of stratum corneum samples from psoriatic lesions and from the heels of normal volunteers were ultrafiltered to yield 10- to 30-kDa fractions. The ultrafiltered psoriatic preparations consistently contained greater neutrophil chemokinetic activity than the normal heel preparations, but in contrast the latter contained markedly greater IL-1 activity than the former. Successive chromatographic purification of psoriatic lesional stratum corneum extracts showed that the neutrophil chemokinetic material previously reported to co-elute with IL-1 activity on reversed phase HPLC, but to be distinct from C5a des arg, could now be separated by anion exchange HPLC into at least four different chemokinetic compounds that were also resolved from the IL-1 activity. The reversed phase HPLC-purified chemokinetic material from psoriatic stratum corneum was also active in a neutrophil chemotaxis assay. These findings show that samples from psoriatic skin lesions contain a group of novel 10- to 30-kDa neutrophil chemoattractant compounds that are distinct from both C5a des arg and IL-1. The contrasting neutrophil chemokinetic and IL-1 activities in psoriatic lesional and normal heel stratum corneum preparations support the finding that the two activities are produced by different compounds. These neutrophil chemoattractant and IL-1-like compounds may be of pathogenic importance in inflammatory skin disease.

Adolescent↗