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Biomedical subjects

L Walker

Publications and source records attributed to L Walker.

At least 163 records · Page 9Linked to original sources
PubMed1988

Demonstration of increased anti-mycobacterial activity in peripheral blood monocytes after BCG vaccination in British school children.

A blood sample was taken from children aged 13-15 years immediately before BCG vaccination and 8 weeks after. The children were tuberculin skin-test negative to PPD-S before vaccination and positive after. Mononuclear cells were separated from the blood, infected with Mycobacterium microti at a low bacterium/monocyte ratio and allowed to form monolayers in microtitre wells. The infected monolayers were rinsed daily and the change in number of live bacteria in monolayers and supernatants was monitored by colony counts on agar. The cells were bacteriostatic during the first day, thereafter growth accelerated in pre-vaccination monolayers. When monolayers received pulsed exposures to autologous lymphocytes that had been incubated with whole dead tubercle bacilli the growth rates of M. microti were increased. However, growth rates in lymphocyte-pulsed monolayers were significantly lower after vaccination than before. It is proposed that this difference reflects the protective effect of vaccination.

Adolescent↗
PubMed1987

Anti-proliferative effects of interferons on Daudi Burkitt lymphoma cells: induction of cell differentiation and loss of response to autocrine growth factors.

Treatment of Daudi B-lymphoblastoid cells with low concentrations of either natural or recombinant human alpha-interferons inhibits cell proliferation and modulates the expression of a number of cell-surface antigens. Using a panel of monoclonal antibodies (MAbs) identifying determinants expressed at the surface of normal plasma cells, and polyclonal antibodies against surface and cytoplasmic immunoglobulin, we have found that growth inhibition is accompanied by plasmacytoid differentiation. Assays of growth stimulation of heterologous cells indicate that the culture medium from interferon-treated Daudi cells contains substantially more B-cell growth factor activity than that from control cells. However, the interferon-treated cells exhibit an impaired ability to respond to both these autocrine factors and exogenous factors produced by another Burkitt lymphoma line. These findings show that, in the case of Daudi cells, growth inhibition by interferons is closely associated with both terminal differentiation and a refractoriness to growth factors. In this system IFN-alpha may therefore be considered to be a B-cell differentiation factor, suggesting a possible basis for the anti-proliferative effects observed with certain human B-cell malignancies.

Antibodies, Monoclonal↗
PubMed1987

Neurotransmitters and memory: role of cholinergic, serotonergic, and noradrenergic systems.

In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study was designed to determine the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Levels of choline acetyltransferase (ChAT), norepinephrine, and serotonin verified lesion effectiveness and selectivity. Chronic changes in serotonergic-2 and beta-adrenergic receptors were also determined. Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different.

Animals↗
PubMed1987

Triggering of B lymphocytes through CD23: epitope mapping and studies using antibody derivatives indicate an allosteric mechanism of signalling.

By using five monoclonal antibodies in reciprocal cross-locking studies, a minimum of three epitope clusters have been defined for the B-cell restricted, activation-associated CD23 antigen. Two of the five antibodies were capable of replacing low molecular weight B-cell growth factor (BCGF) in B-cell co-stimulation assays. These two antibodies belonged to the same epitope group, while non-stimulatory antibodies fell outside this cluster. By prior coating of activated B lymphocytes at 4 degrees, all five CD23 antibodies interfered with the subsequent uptake of BCGF activity onto the cells. However, only the two stimulatory antibodies were capable of inhibiting the absorption of BCGF completely. From one of these antibodies, F(ab')2 and Fab fragments were generated and both were found to be equivalent to whole antibody in their ability to mimic BCGF. Immobilized antibody, however, failed to stimulate over a wide range of concentrations. These findings demonstrate that the ability of certain CD23 antibodies to deliver a growth-promoting signal to activated B cells is independent not only of the Fc portion of the molecule but also of receptor cross-linking. The latter observation is indicative of an allosteric mechanism of triggering, a notion supported by the epitope specificity of activation through CD23. The findings are discussed in relation to the putative natural ligands for CD23 and the way they may influence B-cell function through this receptor.

Antibodies, Monoclonal↗
PubMed1987

Effects of duration of cold storage and gestational age on the insulin secretory capacity of human fetal pancreatic islets.

Studies were performed on human fetal pancreatic tissue to determine viability after long-term cold storage at 0 degrees to 2 degrees C and the effect of gestational age on in vitro insulin secretory capacity. Viability expressed by the insulin secretory capacity was assessed by insulin responses to 2 successive 1 hr static batch incubations. The first incubation (F1) was in low glucose (2mM) medium while the second incubation (F2) included 25 mM glucose and 1 mM 3-isobutyl-1-methylxanthine (IBMX) as potentiator. The fractional stimulatory ratio (FSR defined as F2/F1) and trypan exclusion rates of isolated fetal islets were used as indexes of viability. Cold storage at 0 degrees to 2 degrees C of whole pancreata for period up to 144 hr was not found to alter insulin secretory capacity (FSR-values), but the percentage of dead islets indicated by trypan blue uptake increased. Microscopic examination of dithizone stained pancreatic islets showed intact and well demarcated variable sized islets. Histologically, islets showed well preserved endocrine cells after cold storage for 18 hr followed by culture for 48 hr. Fetal islets isolated from pancreata of 16-18 weeks gestational age were found to have a 2-fold increase in FSR-values when compared to islets isolated from pancreata of 19-24 weeks gestational age. These experiments document the feasibility of obtaining human fetal islet tissue for transplantation at centers widely separated from the site of transplantation. The implication of the enhanced insulin secretory response of islets obtained between 16-18 weeks gestational age remains to be defined.

Cold Temperature↗
PubMed1987

Professional coping.

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Adaptation, Psychological↗