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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 19 recordsLinked to original sources
PubMed1992

Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the endothelial-leukocyte adhesion molecule E-selectin. Dependence of the carbohydrate binding activity on E-selectin density.

Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E-selectin, has been investigated by binding studies using 3H-labeled Chinese hamster ovary cells expressing different levels of the transfected full-length adhesion molecule and a series of structurally defined oligosaccharides linked to the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic glycolipids chromatographed on silica gel plates or immobilized on plastic wells. Evidence is presented for density-dependent binding of the membrane-associated E-selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'-sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a) and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue LNFP-II; there is a threshold density of E-selectin required for binding to these sialylated sequences, and binding to the nonsialylated analogue is a property only of cells with the highest density of E-selectin expression. The presence of fucose linked to subterminal rather than to an internal N-acetylglucosamine is shown to be a requirement for E-selectin binding, and although the presence of sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III sequences substantially enhances E-selectin binding, the presence of 6-linked sialic acid abolishes binding. E-selectin binding is unaffected in the presence of the blood group H fucose (alpha 1-2 linked to galactose to form the Le(b) antigen). However, the binding is abolished when in addition alpha 1-3-linked N-acetylgalactosamine to the galactose (blood group A antigen) is present. These results indicate that some E-selectin-mediated adhesive events may be influenced by blood group status.

Animals↗
PubMed1992

Localized conformational changes in the N-terminal domain of CD4 identified in competitive binding assay of monoclonal antibodies and HIV-1 envelope glycoprotein.

The CD4 antigen is established as a major cellular receptor for the human immunodeficiency virus (HIV). Previous studies have suggested that certain anti-CD4 monoclonal antibodies (MAbs) can inhibit or enhance the binding of the viral envelope glycoprotein gp120 to CD4 by allosteric effects. In the study reported here, 17 anti-CD4 MAbs were tested for their ability to influence the binding of each other to recombinant soluble CD4 in a solid-phase radioimmunoassay. Marked enhancement of binding between specific pairs of MAbs was seen, as well as inhibition or lack of interaction. Enhancement was seen less often when CD4+ cells were used as the target antigen. Information on patterns of enhancement and inhibition permitted grouping of MAbs on the basis of epitope specificity, and this grouping was in agreement with published findings based on X-ray crystallographic studies. These results demonstrate connectivity between epitopes in the first domain of recombinant CD4 and suggest a high degree of flexibility of surface structure. These findings may be of physiological significance both in the normal function of CD4 and in the interaction of CD4 with HIV. The data have implications for research or therapeutic strategies based on recombinant CD4 or CD4 mutants and highlight the problems of interpreting experimental findings based on abrogation of MAb binding.

Antibodies, Monoclonal↗
PubMed1992

A methodology for collecting outcome measures for common hospital conditions.

An eight-month prospective analysis of routinely collected hospital data with 24-week follow-up of mortality and morbidity was carried out at two district general hospitals in Somerset Health District, to test the feasibility of collecting useful and valid outcome measures for two common hospital conditions, strokes and fractured hips. Data were collected on 163 consecutive admissions with a primary diagnosis of stroke (83 cases) or fractured hip (80 cases). At 24 weeks, 38 patients with stroke had died (mortality ratio 46 per cent, 95 per cent C.I. = 35.3-56.7 per cent) and 11 with fractured hip had died (mortality ratio 14 per cent, 95 per cent C.I. = 6.4-21.6 per cent). Seven patients (four with fractured hip and three with stroke) died after 24 weeks and before responding to the NHP questionnaire. One stroke patient could not be traced. Nottingham Health Profiles were received from 106 patients (41 with stroke and 65 with fractured hip). Both groups of patients had problems with physical mobility and lack of energy. Patients with fractured hips were more likely to complain of pain. It is concluded that the methods used to collect outcome measures in this study are widely applicable to other conditions, but the interpretation and comparability of the results require the collection of similar data elsewhere.

Aged↗
PubMed1992

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Aged↗
PubMed1992

Recovery of leukotriene E4 from the urine of patients with airway obstruction.

The urinary excretion of leukotriene E4 (LTE4) was measured in subjects presenting for emergency treatment of airway obstruction. A total of 72 subjects presenting with airway obstruction performed peak flow determinations before and after three treatments with nebulized albuterol given at 20-min intervals. Of these subjects, 22 more than doubled their peak flow rates, while 19 failed to increase their peak flow rates more than 25% during the treatment period. These groups were designated "responders" and "nonresponders," respectively. Urinary LTE4 excretion was determined in 16 of the 22 responders and 12 of the 19 nonresponders as well as 13 normal subjects by precolumn extraction, analytic reversed-phase high-performance liquid chromatography, and enzyme immunoassay. In the normal subjects the urinary LTE4 excretion was significantly (p less than 0.0001) less than the urinary LTE4 measured in the responder subjects, but not less than the urinary LTE4 excretion in the nonresponder group (p = 0.071). The enhanced recovery of LTE4 from the urine of subjects with acutely reversible airway narrowing is consistent with a bronchoconstrictor role for the cysteinyl leukotrienes in spontaneous acute asthma.

Acute Disease↗
PubMed1992

Five DNA tumor viruses undetectable in human retinoblastomas.

Retinoblastoma (RB) is a childhood eye cancer that arises when a retinal cell lacks a functional RB gene. Recent data indicate the transforming proteins of adenovirus, papillomavirus, and the polyomaviruses BK and JC all can bind to the product of the RB gene. Furthermore, adenovirus 12, JC virus, and simian virus 40 are able to induce RB-like tumors in rodents. In view of these findings, 50 human RBs were tested for the presence of five human DNA tumor viruses: adenovirus 12, BK virus, JC virus, and human papillomaviruses 16 and 18. Using the polymerase chain reaction, no viral sequences were detected in 50 RB DNAs. These data provide no evidence that these viruses have an etiologic role in human RB.

Base Sequence↗
PubMed1991

Urinary incontinence: prevalence, need for treatment, and effectiveness of intervention by nurse.

OBJECTIVE: To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN: Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING: One urban and one rural general practice in Somerset. SUBJECTS: 7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION: Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES: Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS: The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS: About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training.

Adult↗
PubMed1991

Clinical use of dreams with latency-age children.

Although various authors have discussed the technical modification required for dream interpretation with children, the basic conceptualization of the psychotherapeutic use of the dream with children has remained virtually identical to that with adult analysands. Examining various sources including formal studies on the nature of children's dreams, clinical case reports and series, and cognitive theories, the authors conclude that a dream arising in the course of a child's therapy must be conceptualized theoretically as a posttraumatic phenomenon. This holds whether or not there has been overt trauma to the child. The reasons for the conceptualization include both the heightened degree of anxiety contained in a dream reported in the course of psychotherapy as well as the specific cognitive abilities of children to contain anxiety and abstract and generalize symbolic meanings. A specific technique based on this conceptualization is then detailed that calls for translation of the dream into more tangible expression (drawing, play, etc.) and a noninterpretative approach. The authors also discuss the more general problem of the nature of insight in children.

Child↗
PubMed1979

A simple technique for harvesting lymphocytes cultured in Terasaki plates.

A simple method has been developed for harvesting lymphocytes from Terasaki microplates based on a culture technique where the plates are inverted and the cells grown on the hanging meniscus of the medium in each well. Sixty individual filter discs were prepared in wells in a polycarbonate harvesting plate. A dry Terasaki plate was used to cut these filters with the harvester acting as a die. The inverted culture plate was then lowered onto the harvester to allow the cells on the meniscus from each well to be absorbed on the appropriate filter disc. The culture plate was then discarded and the cells on the filters washed in the harvester. The wash solutions were removed by suction through holes below each filter. The time taken to harvest the cultures from 60 wells of a plate was 3--5 min.

Cell Separation↗
PubMed1978

Effect of levamisole on metabolism of phagocytic cells.

The effect of levamisole (LMS) on glucose metabolism was studied using a protozoan phagocytic model and human leukocytes. At concentrations of greater than 10 microgram/ml, LMS inhibited glucose metabolism in the protozoan phagocytic model. Glucose metabolism in both the phagocytic model and normal peripheral blood leukocytes was, however, minimally altered when exposed to levels of LMS of less than 10 microgram/ml. In contrast, myeloblasts from a child with leukemia seemed to have increased metabolic activity and 5 microgram/ml of LMS markedly reduced the glucose metabolism. These preliminary studies suggest that LMS can alter glucose metabolism of certain cells and that some malignant cells may be directly inhibited metabolically by LMS.

Child↗