Biomedical subjects

C A Walker

Publications and source records attributed to C A Walker.

At least 19 recordsLinked to original sources

PubMed1998

Mapping of quantitative trait loci on porcine chromosome 4.

A F2 population derived from a cross between European Large White and Chinese Meishan pigs was established in order to study the genetic basis of breed differences for growth and fat traits. Chromosome 4 was chosen for initial study as previous work had revealed quantitative trait loci (QTLs) on this chromosome affected growth and fat traits in a Wild Boar x Large White cross. Individuals in the F2 population were typed for nine markers spanning a region of approximately 124 CM. We found evidence for QTLs affecting growth between weaning and the end of test (additive effect: 43.4 g/day) and fat depth measured in the mid-back position (additive effect: 1.82 mm). There was no evidence of interactions between the QTLs and sex, grandparents or F1 sires, suggesting that the detected QTLs were fixed for alternative alleles in the Meishan and Large White breeds. Comparison of locations suggests that these QTLs could be the same as those found in the Wild Boar x Large White cross.

Animals↗

PubMed1998

Taoism: the way.

Explore the source record for details and available documents.

Female↗

PubMed1996

No association between p53 status and alpha-particle-induced chromosomal instability in human lymphoblastoid cells.

Previous work has demonstrated that alpha-particle irradiation of primary human bone marrow cells leads to the transmission of chromosomal instability in the descendants of the irradiated cell, although there is some interindividual variation. We have extended these studies to human EBV-transformed lymphoblastoid cell lines in order to establish an in vitro model system. The five cell lines analyzed, including one from a Fanconi anaemia patient, exhibited high levels of persistent chromatid aberrations up to approximately 40 cell generations after alpha-irradiation. The p53 status of the cell lines was defined according to whether cellular p53 levels were induced by irradiation, translocated to the nucleus and were able to bind a p53 DNA consensus recognition sequence in vitro. Together with the primary bone marrow cell studies, we conclude that alpha-particle induced chromosomal instability is independent of the p53 status of the cell as defined in these studies.

Alpha Particles↗

PubMed1996

Coalescing the theories of two nurse visionaries: Parse and Watson.

The theories of two nurse visionaries, Rosemarie Rizzo Parse and Jean Watson, are examined for areas of agreement and notable differences. Watson and Parse reject (or hold seriously suspect) traditional, positivistic methods of studying human behaviour and posit their theories as alternatives to the totality paradigm. Since both of these theories, Parse's theory of human becoming and Watson's theory of transpersonal care, borrow heavily from existential phenomenology, major tenets of this philosophic perspective are outlined. Each theory is then described with emphasis on anchoring motifs, concepts, and principles. Next both theories are analysed and critiqued simultaneously. Finally, the theories are applied to a case study with the intent of maximizing their mutual strengths and diminishing their limitations. Coalescence of compatible theories is recommended as a way of enhancing the application of nursing knowledge in practice.

Adult↗

PubMed1995

FIRO-B: the power of love and the love of power.

Factor analysis of FIRO-B data obtained from new software product teams had led to a reformulation of Schutz's ideas on team compatibility. The concept of Group-Warmth as a derivative of the FIRO-B Inclusion and Affection scales was developed and shown to be related to the commercial effectiveness of teams. In a like manner, the FIRO-B constructs of Control-Expressed and Control-Wanted were explored through concurrent factor analysis of 16 PF data. A new interpretation has been given to both FIRO-B Control scales, namely, Assertive-Impulsive.

Adult↗

PubMed1993

Hepato-biliary and renal excretion in mice of charged and neutral gadolinium complexes of cyclic tetra-aza-phosphinic and carboxylic acids.

Tissue distribution of 21 new 157/153Gd complexes was measured at 5 min and 24 hr after an intravenous injection into mice. A complex was judged to be stable in vivo when the percentage of 153Gd retained in the liver and skeleton at 24 hr was comparable with that of 153Gd(DOTA)-. Complexes varied in net charge and lipophilicity and 20 were phosphinic or carboxylic acid derivatives of tetra-aza-cyclo-dodecane. Three anionic, lipophilic complexes were cleared predominantly by the hepato-biliary pathway and were stable in vivo. The remaining 18 complexes were cleared mainly by the kidneys. Of these 18, 1 anionic, 8 neutral, and 3 cationic complexes were stable in vivo. These findings augur well for the future of hepato-biliary and general purpose Gd contrast enhancing agents for MRI.

Animals↗

PubMed1992

67Ga-9N3 uptake by xenografts of human melanotic melanoma in mice.

Tumour uptake of the inert, neutral complex 67Ga-9N3 and the tumour:blood concentration ratio (1,4,7,triazacyclononane-1,4,7, triacetic acid) were measured in mice bearing xenografts of the human melanotic melanoma HX118. Between 1 and 4 h after the injection the tumour:blood ratio increased from 3.5 to 21 and the concentration of 67Ga-9N3 in the tumour decreased from 0.43 to 0.13% g-1. During the first 24 h the concentration of 67Ga-9N3 in the tumour exceeded that in all other tissues except the liver and kidneys. The tumour:blood ratio and tissue distribution of 67Ga-9N3 at 4 h were compared with those of four other complexes. The results indicated that of the five complexes 67Ga-9N3 would be the most suitable for tumour imaging at early times after administration. Imaging would not be restricted to gamma emitting 67Ga as there is also the possibility of using the 9N3 ligand to bind 111In for single photon emission computed tomography (SPECT), 68Ga for positron emission tomography (PET) or even stable Ga for direct in vivo nuclear magnetic resonance (NMR) detection.

Animals↗

PubMed1991

The in vivo release of 90Y from cyclic and acyclic ligand-antibody conjugates.

Yttrium binding ligands DOTA, caDTPA and CT-DTPA were each conjugated to monoclonal antibody B72.3, labelled with 90Y and injected into mice in order to assess the in vivo inertness of the antibody-linked 90Y-ligand complexes. Levels of 90Y in femur shafts of the DOTA-B72.3 mice were low, being approximately 7 and 44%, respectively, of levels in the femur shafts of the caDTPA-B72.3 and CT-DTPA-B72.3 treated mice. This finding demonstrates the greater inertness and by implication the greater suitability for immunotherapy of the DOTA-90Y complex.

Animals↗

PubMed1990

Intraperitoneal infection with scrapie is established within minutes of injection and is non-specifically enhanced by a variety of different drugs.

Single intraperitoneal (i.p.) doses of 16 different drugs were given to mice 2 h before injecting scrapie i.p. Scrapie was injected as serial ten-fold dilutions of standard inocula and the effective titres obtained were used as a measure of the relative efficiency of infection in treated compared to saline injected mice. Despite the wide variety of drugs tested, most of them increased, non-specifically, the efficiency of infection by 0.6 to 2.1 log10 i.p. LD50 units (i.e., 4 to 126-fold), but only when both drug and scrapie were given i.p. The effect was greatest with a 2 h or a 6 h interval suggesting an involvement either of resident peritoneal cells or of elicited cells such as polymorphonuclear neutrophils. There was no increase in the efficiency of infection after intervals of 2 or 7 days when induced macrophages would predominant. The reverse sequence of injections (scrapie-0.5 h-drug) had no effect despite the persistence of high scrapie titre in the peritoneum at the time of drug injection. However, the effect was restored by a second injection of scrapie in the sequence, scrapie-drug-scrapie. It is concluded that scrapie infection is established within minutes of injection but much of the inoculum is associated with peritoneal cells which are irrelevant to pathogenesis. Drugs may enhance the infection of relevant peritoneal cells or their targeting to the visceral lymphoreticular tissues where early replication takes place.

Animals↗

PubMed1989

The role of the spleen in the neuroinvasion of scrapie in mice.

The pathogenesis of 139A scrapie has been studied in CW mice infected intraperitoneally (i.p.), intravenously (i.v.) or subcutaneously (s.c.). In mice splenectomised before i.p. infection, the evidence points to a neuroinvasive pathway from visceral lymph nodes (and other sites of scrapie replication in the peritoneum) to the thoracic spinal cord. However, in non-splenectomised mice, the major neuroinvasive pathway is clearly from spleen to thoracic cord because i.p. incubation periods are shorter and replication in the thoracic cord starts correspondingly earlier than in splenectomised mice. Studies of splenectomy at different times after i.p. infection show that pathogenesis becomes independent of the spleen once infection has initiated scrapie replication in the spinal cord. The simplest interpretation of all the evidence favours the spread of scrapie infection along splenic nerve fibres to the thoracic spinal cord. The same neuroinvasive pathway is suggested by the findings using the s.c. and i.v. routes of infection. In addition it was found that the 100-fold greater efficiency of infection by the i.v. compared to the i.p. route was entirely dependent on the spleen, because splenectomy before i.v. infection reduced its efficiency to the same as that found in i.p. infected (non-splenectomised) mice.

Animals↗

PubMed1989

Pathogenesis of scrapie in mice after intragastric infection.

Infection via the gastrointestinal tract is likely to be a natural route of scrapie infection in sheep. This paper describes the pathogenesis of the 139A strain of scrapie introduced intragastrically (i.g.) into CW mice. There was an almost immediate uptake of infectivity and onset of replication in Peyer's patches which preceded replication in spleen. Splenectomy had no effect on incubation period suggesting that, in contrast to the intraperitoneal route, the spleen plays little or no role in the pathogenesis of 139A scrapie administered intragastrically. Replication in the CNS was first detectable in the thoracic spinal cord and later in brain. The evidence is consistent with neural spread of infection from the gastrointestinal tract, via the enteric and sympathetic nervous systems to spinal cord. Neuroinvasion may be initiated either via infection of Peyer's patches or directly by infection of nerve endings in the gut wall. The latter possibility means that pathogenesis may be completely independent of the lymphoreticular system.

Animals↗

PubMed1989

The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice.

263K is the most widely used strain of agent in scrapie research because it produces very short incubation periods in golden hamsters and exceptionally high infectivity titres in clinically affected brain. 263K is also remarkable in having a very low pathogenicity for mice. Evidence is presented that 263K originated as a mutant that was strongly selected on passage in hamsters. Seven new passage lines have been established in hamsters using well characterized strains of mouse scrapie representing the 'drowsy goat' and SSBP/1 families of scrapie strains, and one natural scrapie source. Considerable differences between scrapie strains were found in hamsters using incubation period criteria alone. There was evidence that the parent strain of 263K might be 79V or a strain like it in the 'drowsy goat' family. Four of the hamster passage lines were established from scrapie strains that had been cloned in mice. Reisolates in mice were compared with original strains. By the criteria used, two of the reisolates were the same as the original strains. Two others were mutants with incubation periods longer than those of their parental strains but the mutants were different from one another. It is concluded that passage between mice and hamsters can select mutants that would otherwise be lost but there is also clear evidence that the genotypic identity of some scrapie strains is preserved on passage between different host species. These findings are important in the search for the putative nucleic acid genome of the scrapie agent.

Animals↗

PubMed1989

Characterization of immunologically important antigens and allergens of Aspergillus fumigatus.

Using a variety of immunochemical methods, including quantitative immuno-electrophoretic techniques, combined with gel filtration and iso-electric focusing, and production of monospecific antisera for identification and affinity purification, 4 major components of Aspergillus fumigatus have now been partially characterized. Numbering of these was derived from a reference allergic bronchopulmonary aspergillosis (ABPA) self-crossed radio-immuno-electrophoresis pattern of reactivity. Two major intracellular/cytoplasmic, concanavalin A (Con A)-binding antigens, Ag 7 and Ag 13, of molecular weights 150-200 and 70 kilodaltons (kD), respectively, were confirmed to be of importance for both ABPA and aspergilloma in specific sandwich enzyme-linked immunosorbent assays. A rapidly released component, Ag 5, of molecular weight 35 kD, proved both antigenic and allergenic, with aspergilloma patients having especially high-titre IgG antibodies. The major allergenic component Ag 3, of molecular weight 24 kD by gel filtration and 18 kD by SDS-PAGE was, like Ag 5, relatively heat-labile and non-Con-A-binding. Interestingly, T cell clones have been identified which respond primarily to an 18-kD fraction.

Allergens↗

PubMed1989

Lymphocyte sensitization to Aspergillus fumigatus in allergic bronchopulmonary aspergillosis.

Peripheral blood mononuclear cell (PBMC) proliferation induced by an extract of Aspergillus fumigatus (AF) was examined in patients with allergic bronchopulmonary aspergillosis (ABPA), all of whom had an immediate skin prick test reaction (SPT) and increased RAST binding to AF, and, for comparison, in individuals without immediate SPT reactivity or increased RAST binding to AF. The proliferative responses of PBMC from the ABPA patients were greater than those from the comparison donors. A substantial proportion of the comparison group, however, showed evidence of a specific immune response to AF, with AF-specific IgG measured by ELISA and specific lymphoproliferative responses. AF-responsive T cell lines and T cell clones were established from both ABPA patients and IgE-negative individuals. These clones, of helper/inducer (CD4+) phenotype, showed antigenic specificity and MHC restriction. The stimulating antigen was determined for four of six clones derived from a skin-prick-test-negative individual, and found to be of Mr 18 kD, possibly the major allergen, 'Ag 3'. ABPA patients showed a marked diminution of the proliferative response during disease exacerbation.

Adult↗

PubMed1988

Pathogenesis of experimental scrapie.

Most of our understanding of the pathogenesis of the unconventional slow infections comes from studies of experimental scrapie in mice and hamsters. After injection by non-neural peripheral routes, pathogenesis necessarily involves the lymphoreticular system (LRS) before the central nervous system (CNS). Available evidence indicates haematogenous spread from the site of injection to the scrapie replication sites in the LRS; later, infection spreads along visceral autonomic nerves from the LRS to the thoracic spinal cord, and thence to brain. The cells in the LRS which are important to scrapie pathogenesis are long lived. Neuroinvasion and spread of infection within the CNS probably involve neuronal pathways. We suggest that disease develops after infection has reached certain clinical target areas in the CNS but only when scrapie replication there has caused sufficient functional damage. Restriction of the replication process in both LRS and CNS is indicated by the occurrence of plateau concentrations of infectivity, especially in some long incubation scrapie models. A remarkable feature of these is that both neuroinvasion and clinical disease occur long after infectivity plateaux have been reached in the LRS and CNS, respectively. We propose that the slowness of scrapie is related to (1) limitations of cell-to-cell spread of infection from LRS to CNS, and (2) limitations on spread between neurons, coupled with restrictions on replication in brain.

Animals↗

PubMed1988

Incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system.

The pathogenesis of intraperitoneally injected ME7 scrapie has been studied in two Sinc genotypes of mice which gave predictable but widely different incubation periods. Comparisons were made with three other mouse scrapie models and one model in hamsters (involving different strains of agent and an untyped isolate from sheep). Average incubation periods ranged from 114 days in the fastest model (263K/hamsters) to 482 days in the slowest (ME7/Sincp7 mice). There were only small differences between models in the times of onset of replication in spleen and cervical lymph nodes. We suggest that the lymphoreticular stage of pathogenesis initiates neuroinvasion in the peripheral nervous system within a few days to a few weeks of infection. Thereafter, pathogenesis appears to be dominated by neural events and replication in brain becomes detectable after approximately 54% of the remaining incubation period has elapsed, irrespective of its length. It is concluded that the differences between incubation periods of the six scrapie models depend mainly on the rate of a continuous process of replication and spread of infection in the peripheral and central nervous system, which is predetermined by scrapie strain and host genotype. The unpredictability of some other scrapie models (and the natural disease) could be explained by additional factors which restrict neuroinvasion from the lymphoreticular system.

Animals↗

PubMed1987

Pathogenesis of scrapie is faster when infection is intraspinal instead of intracerebral.

Previous studies of mice infected peripherally with 139A scrapie showed that scrapie agent initially replicates outside the CNS and that invasion of the CNS occurs several weeks later by neural spread of infection along visceral autonomic fibres to the mid-thoracic cord, and thence to brain. Direct intracerebral infection of brain bypasses the need for extraneural replication and gives shorter incubation periods than peripheral routes. However, it was also found that the duration of the scrapie replication phase in brain, before clinical disease develops, is actually shorter with peripheral routes than with the intracerebral route. We have now investigated this surprising observation using the intraspinal route to reproduce just the neural phase of scrapie pathogenesis seen after peripheral infection. In studies of three strains of scrapie (263K, 139A and ME7) in either hamsters or mice, we have fulfilled the prediction that incubation periods should be shorter after intraspinal infection than after intracerebral infection. Detailed studies of 139A scrapie showed that the shorter incubation period by the intraspinal route could be accounted for by the shorter duration of the scrapie replication phase in brain before clinical disease developed. As a consequence, the severity of the vacuolar lesions in brain at the clinical stage of all three scrapie models was less after intraspinal infection than after intracerebral infection but the severities of vacuolation after intraspinal and intraperitoneal infection were remarkably similar. We speculate that (a) the site of injection (or of invasion) of the central nervous system determines which neural pathways become accessible for the spread of scrapie infection, and that (b) the duration of the neural phase of scrapie pathogenesis is related to the complexity of the pathways between the site of invasion and the clinical target areas in which, it is suggested, scrapie must replicate for disease to develop.

Animals↗

PubMed1987

Temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters.

The interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). The basis of this was investigated using the 139A strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. Cloned scrapie was passaged through hamsters (twice) or rats (thrice) and then reisolated in mice. Large species barrier effects were encountered on mouse-to-hamster and hamster-to-mouse passage resulting in the isolation of a mutant strain, 139-H/M, with properties very different from 139A. In contrast, the strain reisolated from rats was indistinguishable from 139A. However, a large species barrier was encountered at the mouse-to-rat passage but not at the rat-to-mouse passage. It is suggested that the transmission of scrapie between species may be associated with no change in properties or a permanent change in the scrapie genome due to the selection of mutants. A third possibility, the donor species effect, is a temporary change occurring only at first passage in the new host species which is largely or entirely caused by the introduction of material from the previous host. We speculate that the donor species effect could be explained if some host protein forms a functional part of the infectious agent.

Animals↗