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Biomedical subjects

L Lee

Publications and source records attributed to L Lee.

At least 37 records · Page 2Linked to original sources

Determination of the subthreshold state contribution in 13C(alpha,n)16O, the main neutron-source reaction for the s process.

The reaction rate of the stellar reaction 13C(alpha,n)16O, which is currently considered to be the main neutron source for the slow (s) process at low energies, has been rederived using the direct alpha-transfer reaction 13C(6Li,d)17O leading to the subthreshold state at 6.356 MeV in 17O. The contribution of the subthreshold state is found to be much smaller than the currently accepted predictions for the main neutron source of the s process, indicating less of a role of this reaction as the neutron source for the s-process scenario in low-mass stars at the asymptotic giant branch.

Journal Article↗

Sleep-deprived mice show altered cytokine production manifest by perturbations in serum IL-1ra, TNFa, and IL-6 levels.

Serum cytokine and chemokine levels were examined in mice following 36 h of sleep deprivation, or after exposure to a known physical stressor (rotational stress). Significant changes in inflammatory cytokines/chemokines (IL-1beta, TNFalpha, IL-1ra, IL-6, and MIP-1beta, MCP-1) were observed following each manipulation, but qualitative and quantitative differences were seen. Interestingly, only physical stress was associated with measured increases in serum corticosterone levels, and with independent evidence (using in vitro immune allostimulation) for a generalized immunosuppression secondary to the experimental manipulation. Our data suggest that altered cytokine production following sleep perturbation occurs by a different mechanism from that (HPA axis) commonly attributed to stress per se.

Acebutolol↗

Patients' knowledge of and attitudes towards awareness and depth of anaesthesia monitoring.

Awareness during anaesthesia is uncommon (approximately 0.1%), but causes significant anxiety, dissatisfaction and morbidity for patients. Several electroencephalographic monitors hold promise as monitors for awareness. We therefore conducted a survey to evaluate patients' knowledge of and attitudes towards awareness and monitors of anaesthetic depth. Two hundred consenting, preoperative patients completed a seven-item questionnaire. The median number of previous operations was 2 (inter-quartile range, 1-5). Thirteen patients reported an experience which they thought might be awareness (2% of operations performed on the cohort). Only 56% of patients had heard about awareness before and many (35%) of these had heard about it in the media. Many (35%) were uncertain about what might cause awareness. Many (42.5%) were anxious about awareness: female sex and not having heard about awareness before were significant predictors of anxiety. Nevertheless only 34% were willing to pay for a proven awareness monitor if they were at low risk and only 50% if they were at high risk. Perceived risk and a previous awareness experience were significant predictors of willingness to pay for awareness monitoring.

Adult↗

Target words for the Word Stem Completion test in Australian patients.

A robust test that reliably demonstrates implicit memory during general anaesthesia is required. The Word Stem Completion (WSC) test has been used as a measurement tool in a number of recent studies that have detected implicit memory during anaesthesia. However, target words used in the WSC test need to be culturally appropriate in order to maximize the sensitivity of the test. Therefore, fifty postoperative patients with English as a first language were recruited at The Royal Melbourne Hospital in order to assess the frequency of 98 target words in response to a word stem presentation. This generated a list of 32 target words that is suitable for use in studies of implicit memory during anaesthesia in Australian patients.

Aged↗

Eliciting views of patients with head and neck cancer and carers on professionally derived standards for care.

OBJECTIVES: To examine views of patients and carers on the process of care for people with head and neck cancer; to assess whether focus groups are useful in this setting; to compare priorities and standards identified with those published by healthcare professionals; and to incorporate the expressed views into existing national standards. DESIGN: Multicentre study of nine regional focus groups. SETTING: Area covered by two regional health authorities. PARTICIPANTS: 40 patients who had had head and neck cancer and 18 carers. MAIN OUTCOME MEASURES: Views of individuals and groups on standards. Applicability of the method for patients whose appearance and ability to communicate was altered and for recently bereaved carers. Ease of incorporation of views into national and regional standards. RESULTS: Patients and carers participated in discussions on all the principal questions. Opinions were expressed on waiting times, information available to patients, coordination of care, and crisis management. Professionally derived standards were substantially improved by the incorporation of the views of patients and carers. There were no technical problems in carrying out this study on patients with communication difficulties or altered appearance nor with recently bereaved carers. Occasionally, participants said that the meetings were therapeutic. CONCLUSIONS: Professionally facilitated and analysed focus groups are effective in assessing views of patients with cancer and carers on professionally derived standards for care and can be applied in settings traditionally viewed as difficult. Views expressed by patients and carers are powerful motivators for change in the delivery of cancer care.

Caregivers↗

Fetal ear length measurement: a useful predictor of aneuploidy?

OBJECTIVE: To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities. DESIGN: Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography. SUBJECTS: One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester. METHODS: Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined. RESULTS: Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities. CONCLUSIONS: Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

Aneuploidy↗

Training symmetry of weight distribution after stroke: a randomized controlled pilot study comparing task-related reach, Bobath and feedback training approaches.

OBJECTIVE: To determine (1) the most effective of three treatment approaches to retrain seated weight distribution long-term after stroke and (2) whether improvements could be generalized to weight distribution in standing. SETTING: Inpatient rehabilitation unit. DESIGN: Forty asymmetrical acute stroke subjects were randomly allocated to one of four groups in this pilot study. Changes in weight distribution were compared between the 10 subjects of each of three treatment groups (task-specific reach, Bobath, or Balance Performance Monitor [BPM] feedback training) and a no specific treatment control group. One week of measurement only was followed by two weeks of daily training sessions with the treatment to which the subject was randomly allocated. Measurements were performed using the BPM daily before treatment sessions, two weeks after cessation of treatment and 12 weeks post study. Weight distribution was calculated in terms of mean balance (percentage of total body weight) or the mean of 300 balance points over a 30-s data run. RESULTS: In the short term, the Bobath approach was the most effective treatment for retraining sitting symmetry after stroke (p = 0.004). Training with the BPM and no training were also significant (p = 0.038 and p = 0.035 respectively) and task-specific reach training failed to reach significance (p = 0.26). At 12 weeks post study 83% of the BPM training group, 38% of the task-specific reach group, 29% of the Bobath group and 0% of the untrained group were found to be distributing their weight to both sides. Some generalization of symmetry training in sitting to standing was noted in the BPM training group which appeared to persist long term. CONCLUSIONS: Results should be treated with caution due to the small group sizes. However, these preliminary findings suggest that it might be possible to restore postural symmetry in sitting in the early stages of rehabilitation with therapy that focuses on creating an awareness of body position.

Aged↗

Parity violation in proton-proton scattering at 221 MeV.

The parity-violating longitudinal analyzing power, A(z), has been measured in pvectorp elastic scattering at an incident proton energy of 221 MeV. The result obtained is A(z) = [0.84+/-0.29(stat)+/-0.17(syst)]x10(-7). This experiment is unique in that it selects a single parity violating transition amplitude (3P2 - 1D2) and consequently directly constrains the weak meson-nucleon coupling constant h(pp)(rho). When this result is taken together with the existing pvectorp parity violation data, the weak meson-nucleon coupling constants h(pp)(rho) and h(pp)(omega) can, for the first time, both be determined.

Journal Article↗

NKG2D receptors induced by IL-15 costimulate CD28-negative effector CTL in the tissue microenvironment.

Unlike primary T cells in lymph nodes, effector CD8(+) CTL in tissues do not express the costimulatory receptor CD28. We report that NKG2D, the receptor for stress-induced MICA and MICB molecules expressed in the intestine, serves as a potent costimulatory receptor for CTL freshly isolated from the human intestinal epithelium. Expression and function of NKG2D are selectively up-regulated by the cytokine IL-15, which is released by the inflamed intestinal epithelium. These findings identify a novel CTL costimulatory pathway regulated by IL-15 and suggest that tissues can fine-tune the activation of effector T cells based on the presence or absence of stress and inflammation. Uncontrolled secretion of IL-15 could lead to excessive induction of NKG2D and thus contribute to the development of autoimmune disease by facilitating the activation of autoreactive T cells.

CD28 Antigens↗

Routine breast screening for women aged 65-69: results from evaluation of the demonstration sites.

Routine programme data and specially designed surveys from 3 demonstration sites were analysed to determine the implications of extending the NHS Breast Screening Programme (NHSBSP), to include routine invitations for women up to 69 years. All women aged 65-69 and registered with GPs in these areas received routine invitations for breast screening along with those aged 50-64. Overall uptake was 71% in women aged 65-69 compared with 78% in younger women, but was > or = 90% in both groups who had previously attended within 5 years. Recall rates were lower for older women, but with a higher positive predictive value for cancer. The percentages of invasive cancer in different prognostic categories were similar in the 2 age groups. Older women took no longer to screen than younger women. The costs per woman invited or per woman screened were also similar to those for women aged 50-64, whilst the cost per cancer detected was some 34% lower in older women. Breast screening is as cost effective for women aged 65-69 as for those aged 50-64, with a higher cancer detection rate balancing shorter life expectancy. The proposed extension to the national programme will have considerable workforce implications for the NHSBSP and require additional resources.

Aged↗

EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function.

The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans-activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.

Blotting, Western↗

Synthesis of solid-supported mirror-image sugars: a novel method for selecting receptors for cellular-surface carbohydrates.

We introduced a novel method, through mirror-image phage display, for the identification of high-affinity D-peptides to target specific cell-surface carbohydrates. Both 3-deoxy-alpha-L-manno-2-octulosonic acid (L-KDO) and L-sialic acid and an L-sialo-disaccharide have been synthesized and attached to a solid support for selection of high-affinity peptide binders displayed on phages. Our initial studies in this effort produce single-chain Fab sequences and dodecapeptides that bind to sialic acid and KDO with nanomolar and high micromolar affinity.

Amino Acid Sequence↗

Adsorption configuration and local ordering of silicotungstate anions on Ag(100) electrode surfaces.

X-ray reflectivity, cyclic voltammetry, and scanning tunneling microscopy (STM) are used to examine the structure of alpha-SiW12O4(4-) or silicotungstic acid (STA) adsorbed on Ag(100) in acid solution. The voltammetry shows that STA passivates the Ag surface relative to electron transfer to a solution redox species. STM images reveal the formation of a series of lattice structures, one of which can be associated with a commensurate ( radical13x radical13)R33.69 degrees structural model. X-ray reflectivity measurements show uniquely that STA orients with its four-fold axis perpendicular to the Ag(100) surface and that the center of the STA molecule is 4.90 A above the top layer of the Ag substrate. Analysis of bond lengths leads to a footprint of STA on Ag(100), in which the four terminal O atoms are located near the hollow sites and have a Ag-O bond length of 2.06 A. This bond length is consistent with a strong covalent interaction between STA and the Ag surface.

Journal Article↗

Determinants of overall quality of life in secondary progressive MS: a longitudinal study.

Twenty-nine patients with secondary progressive MS underwent monthly assessment with Expanded Disability Status Scale (EDSS), MS Functional Composite (MSFC), MS Quality of Life-54, and cranial MRI over 6 months. Overall quality of life (OQOL) correlated highly with emotional well-being, the mental health composite, health distress, and the physical health composite. In contrast, there was no statistical evidence of consistent correlation between OQOL and EDSS, MSFC, or MR outcome measures.

Adult↗

Strain differences in freezing behavior of PVG hooded and Sprague-Dawley rats: differential cortical expression of cholecystokinin2 receptors.

PVG hooded, but not Sprague-Dawley (SD), rats showed remarkable freezing behavior on cat exposure. Experiments using cDNA microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that cholecystokinin (CCK)2 receptors were expressed to a greater extent in the PVG hooded rats. A CCK2 antagonist, LY225910, inhibited freezing behavior in the PVG hooded rats while a CCK2 agonist, CCK-4, increased freezing behavior in the SD rats. These results strongly suggest that CCK2 receptors mediate the freezing behavior and the differential expression of these receptors underlie the strain difference in such behavior.

Animals↗

Campylobacter jejuni enteritis.

We report the development of Campylobacter jejuni enteritis in a patient with preexisting humoral and cellular immune recognition of C. jejuni antigens. This is one of few studies in which the immunologic status of a person with regard to C. jejuni before and after C. jejuni infection is directly compared, and it is the only study of which we are aware that includes measurements of cellular immunity. The findings may be important to Campylobacter vaccine development efforts.

Antibodies, Bacterial↗

Directional resolution of synthetic holliday structures by the Cre recombinase.

The Cre recombinase of bacteriophage P1 cleaves its target site, loxP, in a defined order. Recombination is initiated on one pair of strands to form a Holliday intermediate, which is then resolved by cleavage and exchange of the other pair of strands to yield recombinant products. To investigate the influence of the loxP sequence on the directionality of resolution, we constructed synthetic Holliday (chi) structures containing either wild-type or mutant lox sites. We found that Cre preferentially resolved the synthetic wild-type chi structures on a particular pair of strands. The bias in the direction of resolution was dictated by the asymmetric loxP sequence since the resolution bias was abolished with symmetric lox sites. Systematic substitutions of the loxP site revealed that the bases immediately 5' to the scissile phosphodiester bonds were primarily responsible for the directionality of resolution. Interchanging these base pairs was sufficient to reverse the resolution bias. The Cre-lox co-crystal structures show that Lys(86) makes a base-specific contact with guanine immediately 5' to one of the scissile phosphates. Substituting Lys(86) with alanine resulted in a reduction of the resolution bias, indicating that this amino acid is important for establishing the bias in resolution.

Base Sequence↗