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Biomedical subjects

V A Anderson

Publications and source records attributed to V A Anderson.

31 records · Page 2Linked to original sources
PubMed1987

Isolation of molecular hybridisation probes for early myeloid lineage RNAs.

Recombinant plasmid cDNA libraries representing the polyadenylated RNAs in the myeloid cell lines KG1 and ML1 have been constructed. The screening protocol has identified several clones which contain sequences homologous to RNAs expressed at high abundance in one or more of the myeloid cell lines KG1, ML1 and HL60. The relative abundances of RNAs homologous to three recombinants, pML15, pKG21 and pKGA/F5 were measured by an RNA dot hybridisation method in total RNAs isolated from peripheral blood leukocytes from leukaemic patients and normal individuals. High levels of these RNAs were observed mainly in ANLL and acute phase CML samples. The data suggest that these probes have the potential to sub-divide the ANLLs and to extend a molecular classification of the myeloid leukaemias.

Acute Disease↗
PubMed1987

The relative abundances of specific RNA sequences can be used to classify the myeloid leukaemias.

The relative concentrations of pCG14 RNA (a myelocyte-specific mRNA), pAM6 RNA (a monocyte-lineage specific marker), and c-myc RNA (present at higher concentrations in more primitive cells) were measured in the RNAs from peripheral blood leucocytes from leukaemic samples and normal individuals. The potential of differences in the relative abundances of these three RNAs in a series of 34 leukaemias was assessed as a means of distinguishing among the myeloid leukaemias. The chronic phase CGL samples were clustered with a high pCG14 RNA, a medium to low c-myc RNA abundance, and a variable pAM6 RNA level. The ANLL samples could be distinguished from the chronic phase CGL by virtue of different relative abundances of these RNAs: low pCG14, medium to high c-myc and a variable pAM6. The acute phase CGL samples showed a variety of relative RNA abundances with some samples sited within the ANLL region. Using samples obtained during the progression of CGL we have shown a shift in the relative abundances of these RNAs from the CGL region towards the ANLL region, and have suggested that the use of these parameters may allow the progression to acute phase to be monitored and, possibly, predicted.

Humans↗
PubMed1985

Activation of complement pathways by univalent antibody derivatives with intact Fc zones.

The ability of two univalent antibody derivatives to invoke complement-mediated lysis of guinea-pig L2C leukemic lymphocytes was investigated. The derivatives were Fab/c from rabbit IgG antibody, in which only one Fab arm is removed from the parent molecule and FabFc in which Fab gamma, from peptic digestion of sheep IgG antibody, is disulfide-bonded to the Fc gamma yielded by papain digestion of an arbitrary IgG. Antibody activity was directed against surface IgM on the target cells. Both derivatives could invoke lysis via the classical pathway in the presence of rabbit complement. Exposure of the cells to the derivatives at 37 degrees C before introducing complement yielded no protective antigenic modulation. At low complement concns the derivatives were more efficient than the parent antibodies at invoking lysis, apparently due to the fact that the derivatives do not cause modulation: it appears that cells can undergo a useful degree of modulation when confronted simultaneously by bivalent antibody and low levels of complement. The Fab/c preparations were also able to invoke lysis by guinea-pig complement. Lysis occurred under conditions where activation took place only via the classical pathway (in dilute complement) or only via the alternative pathway (in the absence of calcium ions, or in C4-deficient guinea-pig serum). The results demonstrate that there is no need for two antigen-binding Fab arms in antibody activation of either the classical or alternative complement pathways. They favour models requiring clustering of Fc regions rather than steric changes which might follow binding of antigen.

Animals↗
PubMed1985

Mutagenicity of drinking water detected by the Tradescantia micronucleus test.

Spring Lake reservoir of Macomb, Illinois, is a typical model of the drinking water supply of some midwestern towns of the United States. Water samples collected periodically in 1980 and 1981 from this lake were tested for mutagenicity using the Tradescantia micronucleus (Trad-MCN) test, a highly sensitive mutagen-detecting bioassay. Water samples from 1981 were also analyzed chemically. The micronucleus (MCN) frequency peaked (12-14 MCN/100 tetrads) in mid-July in both years, as compared with the average frequency (5 MCN/100 tetrads) of the base-line control that was maintained in nutrient solution (prepared with distilled water and pure chemicals). Drinking water from the tap was tested in parallel with lake water, and its mutagenicity tended to fluctuate with the mutagenicity of the lake water.

Cell Nucleus↗
PubMed1983

Tradescantia-Micronucleus (Trad-MCN) test on the genotoxicity of malathion.

The Tradescantia-Micronucleus (Trad-MCN) bioassay was utilized to determine the genotoxicity of Malathion, a common insecticide. Four different treatment procedures were applied: a) absorption of Malathion/water mixture (with or without DMSO and/or S-9) through the stem, b) spraying a Malathion/water mixture onto the plant cuttings in enclosed chambers, c) spraying a Malathion/water mixture on an open population of plants in the greenhouse, and d) absorption of Malathion fumes through the leaves and buds. Most treatments were administered for 6 hr, followed by a 24-hr recovery time. Slides were prepared from the samples and scored for micronucleus (MCN) frequencies. Results of 16 experiments indicated that the genotoxicity of liquid Malathion absorbed through the stem was very low and often masked by high toxicity, causing dead cells in the stem, leaves, and meiocytes. Malathion spray at the dosage of 0.435% in an enclosed chamber or on an open population of plants yielded negative responses. Malathion fumes at dosages of 0.15-0.25% induced significantly higher (0.05) MCN frequencies above the controls and altered the nuclear structure to form unequal sized nuclei and multiple breaks in each of the four cells of a tetrads. It also caused degeneration of nuclei, "protrusions on nuclei," and inhibition of cell growth. Higher dosages (above 0.25%) were toxic.

Animals↗
PubMed1982

The influence of antigen density and a comparison of IgG and IgM antibodies in the anti-complementary modulation of lymphocytic surface immunoglobulin.

Experiments were carried out to determine the influence of antigen density on anti-complementary modulation, defined here as the conferring by anti-immunoglobulin (Ig) of resistance to lysis of guinea pig L2C leukaemic cells varied widely in their quantitative expression of surface membrane Ig as judged by the binding to cells of 125I-labelled Fab' fragments from anti-Ig, and a good correlation between the bulk antigen density and the percentage of cells lysed by anti-Ig plus C was obtained (P=0.02). In the presence of 10 mM sodium azide, which has been shown to diminish the modulation occurring during simultaneous incubations with anti-Ig and C, this correlation was even stronger (P less than 0.001). No zone could be defined in which the level of surface Ig expression was sufficient to serve complement lysis but too low for modulation. Furthermore, both the degrees and rates of modulation occurring on incubation with antibody at 37 degrees C, either before C addition or in the presence of lytic C, were similar for populations of high, low, or intermediate antigen density. Separation of cells by their size or density failed to yield populations differing in either their susceptibility to humoral killing through anti-Ig or their modulating capacity. IgG and IgM antibodies to the L2C cell surface Ig evoked similar levels of killing with syngeneic C, and when compared for their ability to promote anti-complementary modulation, no difference was revealed in either the rate or degree of modulation occurring during incubations at 37 degrees C with the two isotopes. The findings are discussed with particular reference to observations on the modulation of mouse thymus leukaemia (TL) antigens.

Animals↗
PubMed1982

Loss of surface-bound antibody accompanying the anti-complementary modulation of leukemic B cell immunoglobulin: contrasting effects of antibodies directed against idiotypic and constant regions.

Guinea pig L2C leukemic lymphocytes display at their surfaces monoclonal IgM, which when compared with antibody undergoes rapid redistribution and variable endocytosis. One consequence of this is that the cells can prove resistant to lysis by complement subsequently added to the system, a process termed here anti-complementary modulation. We studied quantitatively the extent of antibody loss accompanying the modulation by radioimmunolabeling the cell surfaces with 125I-Fab' gamma fragments from an anti-antibody. Antibody directed against the constant region of the IgG light chain (anti-lambda) gave modulation effective against syngeneic (guinea pig strain 2) complement that closely paralleled the disappearance of anti-lambda from the cell surfaces. Antibody directed against the idiotypic region of the light chain (anti-Id) was as effective as anti-lambda in modulating against syngeneic complement. However, the bulk of the anti-Id was seen by radioimmunolabeling to persist on the surfaces of the resistant cells, even after prolonged exposure at 37 degrees C, and was shown by immunofluorescence to be in a patched configuration. In contrast to the results with syngeneic complement, modulation effective against rabbit complement appeared to have an absolute requirement for clearing of the antibody: thus anti-lambda could modulate, anti-Id could not. The differences observed between anti-lambda and anti-Id could not be accounted for by differences in their isotypic (Ig subclass) composition nor by the numbers of antibody molecules bound. Studies with directly fluoresceinated and 125I-labeled anti-lambda revealed endocytosis rather than shedding was the major route of antibody loss from the cell surfaces over the period of anti-complementary modulation. The findings are discussed in relation to mechanisms that enable leukemic B lymphocytes to escape destruction when confronted by antibody and complement.

Animals↗
PubMed1980

Isolation and characterization of leukaemic B-lymphocytes: influence of anticoagulant on C3-receptor detection, humoral killing and capping of cell surface immunoglobulin.

Guinea pig L2C neoplastic B-lymphocytes processed from leukaemic blood collected into EDTA as anticoagulant exhibited high affinity rosetting for EAC mouse indicator cells. Partial blocking of the C3-receptors was apparent with blood collected into heparin or citrate as anticoagulant. This could be minimized by keeping the temperature at 4 degrees C and avoided by ensuring a high final concentration of citrate (greater than or equal to 40 mM). Results from experiments in vitro suggested that receptor blocking may have been a consequence of complement activation by the L2C cells occurring via the alternative pathway. No injury to the cells was evident with any of the anticoagulants used, and their susceptibility to antibody-dependent complement-mediated lysis was independent of anticoagulant and unaffected by the irregular presence of membrane-bound C3. In experiments where the antibody-induced redistribution of L2C surface immunoglobulin was investigated, it was found that cells processed from blood collected into EDTA showed poor ability to cap and interiorize their surface immunoglobulin in comparison with cells processed from heparinized or citrated blood. Inhibition of capping was found to be dependent on the concentration of EDTA and could be avoided by collecting blood into a large volume of low molarity EDTA as opposed to a small volume of high molarity EDTA. Some practical and theoretical consequences of our observations are discussed.

Animals↗
PubMedDate not supplied

Tradescantia-Micronucleus (Trad-MCN) tests on 140 health-related agents.

The Tradescantia-Micronucleus (Trad-MCN) test is a simple short-term bioassay for various gaseous and liquid forms of chemical agents, and physical agents such as radiation. 140 agents, directly or indirectly related to human health, were screened for their mutagenicity. Plant cuttings of young inflorescences, in which the pollen mother cells undergo various stages of meiosis, were maintained in nutrient solution for experimentation. Treatments were made either by absorption of the soluble agents through the stem, by diffusion of gaseous agents through the leaves and buds, by exposure to internal/external radiation or by in situ exposure to air pollutants. Micronuclei formed from damaged chromosomes served as the indicators of mutagenicity. Results of 140 agents tested are listed in 9 different categories. (1) Carcinogens/mutagens, (2) common beverages, (3) common chemicals, (4) drugs, (5) pesticides, (6) common household chemicals, (7) radiation and radioisotopes, (8) in situ monitoring, (9) complex environmental mixtures. Out of 140 agents tested, 52 showed positive, 20 showed borderline positive responses and 5 showed strong toxicity. Test results of 41 agents in the present study showed 67% congruity with Ames test results found in the literature.

Beverages↗
PubMedDate not supplied

Development of memory and learning skills in school-aged children: a neuropsychological perspective.

While there have been significant theoretical advances in child neuropsychology in recent years, progress in clinical practice has been restricted owing to a lack of well standardized, developmentally appropriate assessment techniques. This paper addresses this issue, with the focus on memory and learning skills. These abilities are targeted because they are frequently impaired following brain damage in childhood, and because they are of central importance to the efficient acquisition of cognitive, educational and social skills throughout childhood. Using a normative sample of 376 children, aged 7.0 to 13.11 years, the paper describes the range of memory and learning skills in childhood, and interprets progress in these skills with reference to neurological and cognitive theory.

Journal Article↗
PubMedDate not supplied

Functional memory skills following traumatic brain injury in young children.

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine recovery of memory function following TBI within the pre-school period. Forty-four children with TBI were divided according to injury severity (mild, moderate, severe), and compared to age and SES matched healthy controls (n = 26). Children were evaluated acutely and at 12 months post-injury using the Rivermead Behavioural Memory Test for Children. Results failed to show a clear dose-response relationship between injury severity and memory function during the acute phase of recovery. However, this relationship developed over time, with greater memory impairments evident for children with more severe TBI by 12 months post-injury. Children with mild TBI exhibited few memory problems.

Analysis of Variance↗
PubMedDate not supplied

The development of pragmatic communication skills in head injured children.

This study investigated the developmental levels of pragmatic language skills in children following head injury (HI), in comparison to their uninjured peers. Participants were 30 head-injured and 19 healthy controls, classified into a 'young' age group, 8-9 years, and an 'old' age group, 11-12 years. Participants were administered the WISC- III, a negotiating requests task and a hint task, the latter two assessing verbal reasoning skills and abilities to be indirect, respectively. It was found that negotiation and hinting strategies were rapidly developing in these age groups, where abilities to hint were less mature for all groups. Results found a main effect for injury on cognitive and functional language tasks, reflected by lower performance levels and inflexibility in reasoning for the head-injured group. Injury sustained at an earlier age consistently predicted poorer performance on the language tasks, complicating the ongoing development of generalized and higher-order communicative skills. Severity of injury did not predict performance on either language task.

Analysis of Variance↗