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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 199 records · Page 11Linked to original sources

Preliminary studies of the interaction between 239PuO2 and cigarette smoke in the mouse lung.

Our current experiments were designed to show whether 12 months' exposure to cigarette smoke enhances the incidence of lung tumours in mice that had previously inhaled 239PuO2. These periods of smoke exposure are almost complete. After death their lungs will be cleared and any nodules found will be sectioned for histopathology. This paper reports the results of two preliminary experiments conducted earlier. The first study showed that mice could tolerate the proposed smoking regime for 3 months, with no sign of ill health in any animal throughout. The major difference found was a reduced growth rate in both smoke- and sham-exposed mice relative to that of cage controls. After 3 months of treatment, histopathology and morphometry of lung sections found only slight smoke-induced changes. These included a reduced proportion of alveolar space and an increased number of pulmonary alveolar macrophages (PAM) per unit area. Bronchopulmonary lavage showed that the PAM from smoke-exposed mice were larger than those from sham-exposed or control mice and that an increased proportion of cells were binucleate. All mice in the second study were initially exposed to 239PuO2, then subsequently divided into three treatment groups as above. Cigarette smoke exposure was shown to inhibit the removal of 239Pu from the lung whilst sham exposure had no effect. Smoke exposure also produced an increase and sham exposure a decrease in lung weights relative to those of cage controls. The latter was probably as a result of their lower growth rate. In our current experiments it is likely that the group receiving 239PuO2, then smoke, will receive a higher radiation dose to lung than those receiving 239PuO2 only. Any increased tumour incidence found will be considered in conjunction with this evidence.

Animals↗

Expression of the Epstein-Barr virus gp350/220 gene in rodent and primate cells.

The gene encoding the Epstein-Barr virus envelope glycoproteins gp350 and gp220 was inserted downstream of the cytomegalovirus immediate-early, Moloney murine leukemia virus, mouse mammary tumor virus, or varicella-zoster virus gpI promoters in vectors containing selectable markers. Host cell and recombinant vector systems were defined which enabled the isolation of rodent or primate cell clones which expressed gp350/220 in substantial quantities. Continued expression of gp350/220 required maintenance of cells under positive selection for linked markers and periodic cloning. gp350/220 expressed in various host cells varied slightly in electrophoretic mobility, probably reflecting differences in glycosylation. Insertion of a stop codon into the gp350/220 open reading frame, upstream of the putative membrane anchor sequence, resulted in efficient secretion of truncated gp350 and gp220 from rat pituitary (GH3) cells. gp350/220 expressed in mammalian cells is highly immunogenic and elicits virus-neutralizing antibodies when administered to mice.

Animals↗

A single autoantigen in Goodpasture's syndrome identified by a monoclonal antibody to human glomerular basement membrane.

A mouse monoclonal antibody (P1) to the autoantigenic component of human glomerular basement membrane (GBM) was used to study the immunochemistry and tissue distribution of the Goodpasture antigen and the specificity of the human autoimmune response in Goodpasture's syndrome (anti-GBM disease). In solid phase assays, monoclonal antibody P1 bound to collagenase-solubilized human GBM (the ligand used in assays for human autoantibody), but not to other biochemically defined components of basement membrane. On Western blotting, P1 bound to the same 6 bands in solubilized GBM (between 26 and 58 kilodaltons with major bands at 26 and 54 kilodaltons) that were recognized by sera from all 42 patients studied with anti-GBM disease. Preincubation with sera from 8/8 patients blocked the subsequent binding of P1 from 83 to 89% on densitometer scanning of the Western blot; and preincubation with P1 blocked the binding of sera from 6/6 patients from 58 to 89%. Indirect immunofluorescence and immunoperoxidase studies revealed that the pattern of binding of P1 was identical to that of antibody eluted from the kidneys of a patient with Goodpasture's syndrome; there was linear binding to GBM, Bowman's capsule, and distal tubular basement membrane. In addition, P1 bound to basement membranes in lung and choroid plexus, and to membranes of the lens capsule, choroid, and retina of the eye and cochlea, but not to other organs studied. It is concluded that there is a single major autoantigenic component of human GBM (the Goodpasture antigen), which is present on fragments of different molecular weight in the collagenase digest. This antigen is distributed throughout well-defined basement membranes known to be involved in both Goodpasture's and Alport's syndromes. Human anti-GBM antibodies bind to the same (or closely related) determinants which are recognized by P1, demonstrating that the autoimmune response in Goodpasture's syndrome is of highly restricted specificity.

Anti-Glomerular Basement Membrane Disease↗

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Community Health Nursing↗

Multiple intestinal atresia and amyoplasia congenita in four unrelated infants: a new association.

Four unrelated infants with multiple segments of nonduodenal intestinal atresia and amyoplasia congenita are described. The extreme rarity of each of these conditions as a single entity indicates that their concurrent incidence in four separate unrelated patients is of significance with respect to pathogenesis. The nature of the relationship between the two conditions is unknown.

Arthrogryposis↗

Factor analysis of the Wechsler Memory Scale: is the associate learning subtest an unclear measure?

A factor analysis of the Wechsler Memory Scale (WMS) with 30-minute delayed recall scores (percent retained) for the Logical Memory, Visual Reproduction, and Associate Learning subtests indicated that this variant of the WMS taps different types of learning and memory for new material. With regard to the verbal learning/recall subtests, Logical Memory appears to be related to attention/ concentration ability, while Associate Learning is relatively independent. The results also showed that both the easy and hard items from Associate Learning tap the same ability, providing evidence that this subtest is a measure of rote verbal learning. These results support the clinical utility of the WMS with delayed recalls in neuropsychiatric populations.

Journal Article↗

Translocation of 239Pu in mice following inhalation of sized 239PuO2.

This study showed that when SAS/4 mice were exposed to sized 239PuO2 only about 0.5% of the 239Pu was translocated from lung to other organs. The fraction of 239Pu translocated appeared to be independent of the particle size of the administered 239PuO2 within the range of AMADs investigated (0.8-2.2 microns). The distribution of translocated 239Pu was similar to that observed with other species in that most of the activity was associated with the lung-associated lymph nodes followed by bone and liver. The fraction of 239Pu translocated was comparable to that found in studies with rats (ICRP72) but less than that found in more extended studies with beagle dogs.

Aerosols↗

A monoclonal antibody based solid-phase enzyme-binding assay to measure levels of placental alkaline phosphatase in serum of women during pregnancy.

Monoclonal antibodies raised against highly purified placental alkaline phosphatase (PALP) reacted specifically with PALP and were found not to cross-react with the liver, kidney and intestinal enzymes. One of these antibodies (AP-3) was selected to develop an enzyme-binding assay to measure levels of PALP in the sera of 11 women throughout pregnancy. PALP activity rose sharply after 28 weeks of gestation reaching a peak at delivery followed by an immediate drop within 4 days to values approaching non-pregnant levels. The potential of using this assay as an index of placental function to monitor progress of a pregnancy is discussed.

Alkaline Phosphatase↗

The distribution of dust in the rat lung following administration by inhalation and by single intratracheal instillation.

A comparison was made of the distribution of dust in the rat lung following its administration by inhalation and by a single intratracheal instillation. Due to the wide variety of instillation techniques, an "average" method was adopted based on the results from a survey of 15 laboratories in Europe and the USA. Novel techniques were developed to quantify the distribution of dust within the lung both microscopically and macroscopically. The distribution of dust obtained by instillation was shown to be much less homogeneous that that obtained by inhalation and penetration to the periphery was minimal. The effects of (a) changing the volume of suspension, (b) changing the concentration of the suspension, and (c) introducing air into the syringe were investigated. Although the use of air in the syringe was beneficial, none of the other modifications effected any improvement in the distribution. The difference in distribution following inhalation and instillation leads to the conclusion that the latter may be of use in establishing the nature and comparative response of the lung to different dusts, but not for establishing an absolute dose-response relationship. It is recommended that no more than 1 mg of fibrous or 5 mg of nonfibrous dust be given in a single instillation to adult rats.

Animals↗

The enigmatic asbestos body: its formation and significance in asbestos-related disease.

It is well established that many different types of fibre, both organic and inorganic, can become coated with ferritin in lung to give ferruginous bodies. The presence of such bodies is one factor which is taken into account in assessing cases with asbestos-related disease for the purpose of compensation, although their presence is only an indication of past exposure and not proof of the causative role of asbestos. In this paper, evidence relating to the formation of ferruginous bodies in human lung is reviewed, to identify factors which predispose certain types and dimensions of fibre to become coated. Work with experimental animals is also summarised to give some indication of the time course of body formation.

Animals↗

Colonic ischaemia and anastomotic healing.

The leakage rate of colonic anastomoses may be as high as 13%. A good blood supply is of paramount importance. However tissue perfusion may be at risk in the elderly and in low colorectal anastomoses. We have tested the effect of isoxsuprine, an agent which reduces blood viscosity, and is an alpha-adrenergic antagonist and beta-adrenergic agonist, on the healing process in normal and ischaemic rat colon. Both bursting pressure and hydroxyproline concentration were significantly improved in compromised ischaemic colon in animals treated with isoxsuprine. Isoxsuprine may improve healing in poorly perfused colonic anastomoses.

Animals↗

Analysis of asbestos fibers and asbestos bodies in tissue samples from human lung. An international interlaboratory trial.

In order to compare methods of counting asbestos fibers in lung tissue, seven laboratories participated in an interlaboratory trial in which tissue samples from five human lungs were analyzed. In some laboratories, fiber concentrations were assessed with the light microscope and, in others, with either scanning or transmission electron microscopes. Within each laboratory the ranking of the results was similar, but there were marked differences in the absolute values obtained by the different laboratories. It is concluded that the laboratories participating in this trial appear to produce internally consistent results, but there is difficulty in directly comparing results from one laboratory to the next.

Aged↗

Five groups of antigenic determinants on DNA identified by monoclonal antibodies from (NZB X NZW)F1 and MRL/Mp-lpr/lpr mice.

A library of monoclonal antibodies (MCA) reactive with DNA was derived from mice with lupus-like disease. The combining reactions of the antibodies was determined by ELISA, precipitation assay and indirect immunofluorescence assay on cells. On the basis of their reactions in these assays, the MCA have been classified into five taxonomic groups. MCA in Group I react with conformational determinants on double-stranded DNA (dsDNA); those in Group II with conformational backbone-dependent sugar-phosphate determinants on dsDNA and single-stranded DNA (ssDNA); those in Group III with determinants predominantly expressed on ssDNA; those in Group IV with base-dependent determinants on ssDNA, and those in Group V with determinants on both DNA and RNA. It is concluded that antibodies which react with DNA are collectively of limited heterogeneity with regard to their specificity. The study illustrates how, upon traditional interpretation, different assay systems may give discordant results in the assignment of specificity to antibodies reactive with DNA.

Animals↗

A key role for fibronectin in the sequential binding of native dsDNA and monoclonal anti-DNA antibodies to components of the extracellular matrix: its possible significance in glomerulonephritis.

The interactions of DNA, monoclonal anti-DNA autoantibodies and isolated purified components of the extracellular matrix (ECM) were studied in a solid phase model system. Binding of DNA to each of the components was assessed using monoclonal antibody and enzyme conjugated antiglobulin in direct binding and inhibition assays. Each of the genetically distinct collagens (Types I-IV), proteoglycan monomer and laminin, bound ssDNA, but dsDNA bound significantly only to fibronectin. When used in an inhibition system, fibronectin linked DNA and anti-DNA antibodies to the collagens; it had a differential effect on the binding of ssDNA and dsDNA to a Type IV collagen matrix, the most striking feature being a 100 fold increase in dsDNA binding to Type IV collagen in the presence of fibronectin. It is likely that fibronectin binds dsDNA to collagen by separate binding domains for these molecules, and that this may be involved in the deposition of DNA in kidneys in some forms of glomerulonephritis.

Animals↗

Shared idiotypes are expressed on mouse and human anti-DNA autoantibodies.

The expression of common idiotypes on human and mouse anti-DNA monoclonal autoantibodies made by hybridomas was examined by their competitive binding to anti-idiotype antibodies. Some murine autoantibodies inhibited the binding of a human anti-DNA autoantibody 16/6 to monoclonal or polyclonal anti-idiotypic antibodies. Another human antibody (134) was not inhibited in its binding to homologous anti-idiotypic antibodies. The expression of the human 16/6 idiotype on mouse antibodies was restricted to those that had a specificity similar to the 16/6 antibody itself, their major properties being that they reacted more strongly with single stranded DNA (ssDNA) than double stranded DNA (dsDNA). One mouse antibody expressing the 16/6 idiotype also bound weakly to RNA. The results imply structural similarities between the binding sites of the antibodies in the two species, and are consistent with evolutionary conservation of V genes coding for primitive ancestral antibodies that react with DNA and become diversified through somatic mutation.

Animals↗