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Biomedical subjects

L A Williams

Publications and source records attributed to L A Williams.

At least 55 records · Page 3Linked to original sources

Identification of a novel dendritic cell surface antigen defined by carbohydrate specific CD24 antibody cross-reactivity.

Dendritic cells (DC) are characterized as leucocytes that lack mature lineage specific markers and stimulate naive T-lymphocyte proliferation in vitro and in vivo. The mouse heat stable antigen (HSA) participates in T lymphocyte co-stimulation and is expressed by DC isolated from thymus, skin and spleen. The human HSA homologue, CD24, is predominantly expressed by B lymphocytes and granulocytes, but its expression on DC has not been studied in detail. CD24 clearly participates in B-lymphocyte signalling but co-stimulatory activity for T lymphocytes has not yet been described. We have examined the expression of CD24 on human peripheral blood DC populations isolated directly or following in vitro culture. The CD24 antigen was absent from blood DC however, cross-reactive sialylated carbohydrate epitopes were detected on DC with some CD24 monoclonal antibodies (mAb). These CD24 mAb define a protein surface antigen, which is expressed by an immature or resting subpopulation of peripheral blood DC and is down-regulated following activation differentiation in vitro.

Antibodies, Monoclonal↗

Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis.

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.

Arthritis, Rheumatoid↗

Impact of permethrin impregnated bednets on child mortality in Kassena-Nankana district, Ghana: a randomized controlled trial.

A community-based randomized, controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana, between July 1993 and June 1995, to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use. The district around Navrongo was divided into 96 geographical areas and in 48 randomly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months. A longitudinal demographic surveillance system was used to record births, deaths and migrations, to evaluate compliance and to measure child mortality. The use of permethrin impregnated bednets was associated with 17% reduction in all-cause mortality in children aged 6 months to 4 years (RR = 0.83; 95% CI 0.69-1.00; P = 0.05). The reduction in mortality was confined to children aged 2 years of younger, and was greater in July-December, during the wet season and immediately after (RR = 0.79; 95% CI 0.63-1.00), a period when malaria mortality is likely to be increased, than in the dry season (RR = 0.92, 95% CI 0.73-1.14). The ready acceptance of bednets, the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implications for programmes to control malaria in sub-Saharan Africa.

Bedding and Linens↗

Impact of MRI on a knee arthroscopy waiting list.

As part of a waiting list initiative, magnetic resonance imaging (MRI) scans were arranged for 69 patients waiting for knee arthroscopy. All patients had a clinical diagnosis of a meniscal tear. With 11 non-attenders, 58 scans were performed. Of the patients scanned, 35 had demonstrable meniscal tears, and five patients had other pathology on their scans. All patients were reviewed clinically after their scans, and 24 patients were removed from the waiting list. After a further 9 months, only one of the 24 patients removed had been re-listed for therapeutic arthroscopy. This initiative proved a cost-effective method of reducing waiting times for knee arthroscopy.

Arthroscopy↗

Activation of human peripheral blood dendritic cells induces the CD86 co-stimulatory molecule.

Maximal T lymphocyte responses require presentation of antigen by major histocompatibility complex molecules and delivery of one or more co-stimulatory signals. Interaction of the CD28 molecule on T lymphocytes with its ligands on antigen-presenting cells (APC) initiates a critical co-stimulatory pathway inducing T lymphocyte proliferation and cytokine secretion. Dendritic cells (DC) are potent APC for a primary T lymphocyte response and potential CD28/CTLA-4 ligands on DC are, therefore, of particular functional relevance. In these experiments, the expression and function of the CD28/CTLA-4 ligands B7.1 (CD80) and B7.2 (CD86) were examined on human blood DC. Resting DC populations directly isolated by immunodepletion of lineage marker-positive cells lacked cell membrane expression of CD80 and expressed little or no CD86, although CD86, but not CD80 mRNA was detected by reverse transcription-polymerase chain reaction analysis. In contrast, low-density DC isolated after culture in vitro strongly expressed CD86 surface protein, but expressed limited or no CD80, although mRNA for both molecules were detected. Short-term culture of directly isolated DC up-regulated both CD80 and CD86 expression. Analysis of the kinetics of CD28/CTLA-4 ligand induction showed that surface CD86 was present within 8 h, whereas CD80 antigen was first detected after 24 h of culture. The functional importance of CD28/CTLA-4 ligand up-regulation on DC during T lymphocyte interactions was demonstrated by the ability of both CTLA-4Ig and CD86 monoclonal antibodies (mAb), but not CD80 mAb, to block an allogeneic mixed lymphocyte reaction stimulated by DC populations initially negative for CD80 and CD86. These results demonstrate that CD86 is both the earliest and functionally the predominant co-stimulatory CD28/CTLA-4 ligand on DC.

Abatacept↗

MRI in the management of tibial plateau fractures.

Twenty-one consecutive patients with fractures of the tibial plateau were investigated by standard radiography and magnetic resonance imaging (MRI) before treatment. It was found that MRI was more accurate in determining the classification of the fracture, in the identification of previously 'occult' fracture lines, and in accurate measurement of displacement and depression of fragments. This resulted in a change in the classification of 10 fractures (47.6 per cent) and so a change in the management of four patients (19 per cent). In addition, MRI permits the reliable identification of associated intra- and periarticular soft tissue injuries pre-operatively for the first time in this group of injuries, seen to be present in 47.6 per cent of this series. This is higher than previously reported. No problems were encountered with the imaging technique, and in view of the significant effect on patient management, the authors now consider it to be the imaging method of choice.

Adolescent↗

Acaricidal and insecticidal activities of cadina-4,10 (15)-dien-3-one.

The novel assignment of 13C and 1H NMR data for cadina-4,10(15)-dien-3-one obtained from Hyptis verticillata is presented. The study revealed that cadina-4,10(15)-dien-3-one possesses chemosterilant activities against the economically important cattle tick, Boophilus microplus, and toxic action against adult Cylas formicarius the most destructive pest of sweet potato (I pomoea sp.).

Animals↗

Facial rejuvenation.

Facial rejuvenation includes several operations: rhytidectomy, rhinoplasty, blepharoplasty, mentoplasty, brow lift, chemical face peel dermabrasion, and collagen injections. The nurse's role begins with identification of expectations of the procedure. The operations described take the surgeon a few hours. Yet the ultimate success occurs over the weeks of postoperative care. Because most operations are performed on outpatient basis, the nurse's role is crucial in preparing the patient for self-care.

Dermabrasion↗

Pathways of lysozyme evolution inferred from the sequences of cytochrome b in birds.

A reliable phylogeny relating the major groups of Galliformes was sought in order to shed light on an unusual case of coupled amino acid replacements in the lysozymes c of these birds. The New World quail and the African guinea fowl share a unique trio of amino acids at three internal positions but have been separated phylogenetically by the majority of trees based on morphological characters. Alternative hypotheses based on molecular data have suggested an arrangement that would be more parsimonious with regard to the lysozyme data. The entire mitochondrial cytochrome b gene (1,143 bp) was amplified via the polymerase chain reaction (PCR) and sequenced for nine galliforms and a representative anseriform to provide DNA sequence data for a phylogenetic reconstruction. The mode and tempo of change in these sequences were analyzed to determine the characters most appropriate for phylogenetic reconstruction. Our results place the New World quail outside all other representative game birds except the cracids. Although in conflict with various morphological analyses, this finding is consistent with the results of DNA-DNA hybridization studies. A model to account for the coupled replacements in the lysozymes is presented. Our results also suggest a rapid but ancient radiation among the Galliformes such that the majority of cytochrome b sequence differences among taxa have accumulated on the terminal branches of the reconstructed phylogenetic trees.

Amino Acid Sequence↗

Effect of membrane lipids on the lactosylceramide molecular species specificity of CMP-N-acetylneuraminate:lactosylceramide sialyltransferase.

It has previously been shown that when the molecular species specificity of rat liver Golgi CMP-N-acetylneuraminate:lactosylceramide alpha 2,3-sialyltransferase was determined, using as the substrate lactosylceramide (LacCer) incorporated into liposomes prepared with rat liver Golgi lipids, the enzyme showed a pronounced variation in activity towards the various molecular species of LacCer (J. Lipid Res. 1989. 30: 1789-1797). In this paper, -the LacCer molecular species specificity of sialyltransferase from neuroblastoma NB2a cells was examined using five naturally occurring and three synthetic molecular species of LacCer. The enzyme activity was determined by following the formation of [14C]GM3 from CMP-[14C]neuraminic acid and individual molecular species of LacCer incorporated into liposomes. Nonspecific lipid transfer protein was included in the enzyme assay to facilitate the transfer of LacCer and other lipids between the liposomes and the membrane where sialyltransferase is located. In these enzyme assays the liposomes contained approximately 10 times more lipid phosphorus than either the microsomal fraction of NB2a cells or the Golgi fraction of rat liver. Thus, in the presence of nonspecific lipid transfer protein, the lipid composition of the membrane where sialyltransferase is located was modified to resemble the lipid composition of the liposomes. When the molecular species specificity of NB2a cell sialyltransferase was determined with LacCer incorporated into liposomes prepared with NB2a cell lipids, the enzyme showed no specificity towards the various molecular species of LacCer. However, when the molecular species specificity of NB2a cell sialyltransferase was determined with LacCer incorporated into liposomes prepared with rat liver Golgi lipids, the enzyme showed a variation in activity towards the various LacCer molecular species similar to that observed with the liver Golgi enzyme using liposomes prepared with liver Golgi lipids. Likewise, when the molecular species specificity of rat liver Golgi sialyltransferase was determined with LacCer incorporated into liposomes prepared with NB2a cell lipids, the liver enzyme then showed no specificity towards the various molecular species of LacCer. These results indicate that the lipid environment of the membrane can alter the molecular species specificity of sialyltransferase towards its lipid substrate, LacCer.

Animals↗

Heel pain in the older patient.

Older Americans are the fastest growing segment of the US population. For this group, mobility is a significant factor in individual well-being. Heel pain is primarily a symptom found in adults, and like most health problems, increased age has a compounding effect on most disease processes. If heel pain becomes the cause of immobility in an older patient, significant consequences may arise. The true prevalence of heel pain in older individuals is not known precisely. The frequency may lie between 12.5% and 15% on the basis of reports in the literature. The scientific basis of these figures, however, is open to question. No one method of organizing heel pain according to a causative agent or condition is accepted universally. A review of the literature, however, reveals that most reporters ultimately include the same elements in whatever schema they use. In general terms, management of heel pain, regardless of the cause, can be organized according to noninvasive to invasive treatment methods. The authors have found the categories of mechanical, pharmacologic, and surgical to be useful. Selection of a therapeutic method is based on the patient's specific physical circumstance and social situation.

Aged↗

Covert bacteriuria: long term follow up.

In a longitudinal prospective study 58 schoolgirls with covert bacteriuria were followed up for an average of 11.2 years (range 8.8 to 13.5 years). Intravenous urography was carried out at the start of the study (aged 4 to 11 years) and after completion of the follow up period (aged 14.8 to 22.3 years). After random allocation 27 of these girls received intermittent treatment for covert bacteriuria for the first four years and the control group received no treatment. The effect of covert bacteriuria, treatment, vesicoureteric reflux, and reflux nephropathy at presentation on the final renal length, progression of scarring, and development of new scars was analysed. No new scars were found in girls with bilaterally normal kidneys. In girls with reflux nephropathy, three kidneys showed progression of existing scars and two kidneys developed new scars. It was shown that final renal length was not influenced by vesicoureteric reflux or treatment, but reduced renal length at final assessment was associated with the presence of kidney scarring at initial assessment.

Bacteriuria↗

Pitfalls of bone scintigraphy in suspected hip fractures.

In a review of 2617 patients who were admitted with a suspected fractured neck of femur over a period of five years, 213 had normal or equivocal plain radiographs, and were subsequently investigated by bone scintigraphy. Normal scans were obtained in 127 (60%) cases. Of the remaining 86 cases, 82 (38%) were reported to show fractures of the proximal femur, three showed pubic ramus fractures, and one acetabular fracture was demonstrated. Review and follow-up has revealed eight false positive and two false negative scans. The various factors accounting for these errors are considered, and the clinical implications discussed. Careful analysis of accompanying plain radiographs is stressed when interpreting scintigrams.

Aged↗

Labelling of tumour cells with a biotinylated inhibitor of a cell surface protease.

Our objective has been to prepare a biotinylated affinity probe for the active centre of a protease associated with the surface of tumour cells. We employed three model systems in which easily recognisable tumour cells containing the active protease were used as targets for the biotinylated affinity probe. These were: squamous cell carcinoma, leukaemia cells in muscle and outgrowths of prostate carcinoma cells grown in three dimensional collagen gels. The presence of the bound biotinylated affinity probe was demonstrated by its ability to bind Texas-red labelled streptavidin with the results that the tumour cells exhibited red fluorescence. This binding was shown to be competitive with 9-amino acridine, a compound known to bind to the active centre of the target protease. This technique depends upon the affinity of the active centre of an enzyme for a competitive inhibitor and therefore should be applicable to other enzyme systems employing suitable ligands for their active centres.

Affinity Labels↗