A clinical and radiographic variant of Wernicke-Korsakoff syndrome in a nonalcoholic patient.
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Adenocarcinoma↗
Biomedical subjects
O Williams
Publications and source records attributed to O Williams.
Exhaled nitric oxide in chronically ventilated preterm infants.
Exhaled nitric oxide (eNO) levels were measured in eight ventilated infants, mean gestational age 25.8 (SD 1.7) weeks and postnatal age 55 (SD 39) days, before and after three days of dexamethasone treatment. The eNO levels fell from a mean of 6.5 (SD 3.4) to 4.2 (SD 2.6) parts per billion (p = 0.031) and the mean supplementary oxygen levels from 62% to 45% (p = 0.0078).
Anti-Inflammatory Agents↗
Extubation failure due to phrenic nerve injury.
A 26 week gestation infant had an increasingly elevated right hemidiaphragm following drainage of bilateral pleural effusions and failed extubation on numerous occasions. Electric stimulation of the phrenic nerves revealed absent activity on the right, indicating phrenic nerve injury from chest tube drain insertion. Diaphragmatic plication was performed and the infant successfully extubated four days later.
Chest Tubes↗
Tumor necrosis factor-related apoptosis-inducing ligand in T cell development: sensitivity of human thymocytes.
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in various tumor cell lines, whereas most primary cells seem to be resistant. These observations have raised considerable interest in the use of TRAIL in tumor therapy. Yet little is known about the physiological function of TRAIL. This is particularly the case in the immune system, where TRAIL has been suggested by some to be involved in target cell killing and lymphocyte death. We have developed a panel of mAbs and soluble proteins to address the role of TRAIL in lymphocyte development. These studies demonstrate activation-induced sensitization of thymocytes to TRAIL-mediated apoptosis and expression of the apoptosis-inducing TRAIL receptors. However, with the use of several model systems, our subsequent experiments rule out the possibility that TRAIL plays a major role in antigen-induced deletion of thymocytes. In contrast to thymocytes, there is no up-regulation of TRAIL receptors in peripheral T cells on activation, which remain resistant to TRAIL. Thus, susceptibility to TRAIL-induced apoptosis is controlled differently by central and peripheral T cells.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Elevated Bcl-2 is not a causal event in the positive selection of T cells.
T cell development is characterized by the induction of apoptosis in most immature thymocytes and the rescue from apoptosis of a small proportion of cells by the process of positive selection.Up-regulation of the anti-apoptotic molecule Bcl-2 is associated with thymocytes undergoing positive selection and a bcl-2 transgene promotes the generation of mature T cells. In contrast,mice transgenic for the pro-apoptotic molecule Bax show impaired T cell maturation. We have used fetal thymic organ culture to determine the action of Bcl-2 and Bax on positive selection of thymocytes. Our data show that Bcl-2 and Bax do not alter the number of thymocytes positively selected by a defined peptide ligand. This implies that Bcl-2 and Bax alter the production of mature T cells in vivo by influencing thymocyte viability rather than by direct action on positive selection. It also presents a solution to the 'chicken-and-egg' scenario relating to Bcl-2 up-regulation and positive selection. The data suggest that the up-regulation of Bcl-2 associated with T cell maturation is a consequence of positive selection rather than a cause of it.
Animals↗
The role of molecules that mediate apoptosis in T-cell selection.
The T-cell repertoire is generated as a result of selection processes that happen in the thymus. The molecular basis of these processes is beginning to be elucidated and many of the molecules identified have a role in regulating cell death. These molecules range from orphan nuclear receptors and transcription factors to cyclin-dependent kinase 2 and Bcl2 family members.
Animals↗
'Say no to sex; great idea but...'.
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Adolescent↗
Screening for sexually transmitted infections in children and adolescents in the United Kingdom: British Co-operative Clinical Group.
Our objectives were (1) to assess the number of young people aged under 16 years attending genitourinary medicine (GUM) departments in the UK in 1998; (2) to identify clinical activity and policy; (3) to determine the knowledge and training needs of healthcare professionals within GUM providing care for this client group. In July 1999 a questionnaire was circulated via the 18 regional British Co-operative Clinical Group (BCCG) representatives to the consultants in charge of all 197 main GUM departments in the UK. One hundred and sixty out of 197 (81%) completed questionnaires were returned and analysed. The reported number of under-16-year-olds attending in 1998 varied considerably between clinics; for females ranging from 0 to 256 and for males between 0 and 50, with a male to female ratio of 1:4.4. The majority of responding clinics, 139/160 (87%) had been involved in the screening of abused children/adolescents for sexually transmitted infections (STIs). Most clinics were prepared to screen for STI (86%), HIV test (79%) and assess contraceptive needs (50%) in this age group. Staff involved in care included health advisers (74), nurses (59), and doctors (138) in the responding clinics. Only 31/160 clinics (19%) had a written policy for the management of children/adolescents attending their clinic. The majority of respondents were aware of their child protection policy [122/154 (79%)] and designated child sexual abuse doctor, [125/157 (80%)] in their district. When questioned on previous and current training needs, 134/160 (84%) respondents identified their need for further training in the area of adolescent sexual health and 124/160 (78%) in child sex abuse. The publication Physical Signs of Sexual Abuse in Children, was known to 112/160 (70%) respondents, of whom 58/112 (52%) who answered this question had read the publication. Genitourinary physicians in the UK are aware of the increasing number of children and adolescents accessing their services, and recognize the need to identify those in abusive situations. Written policies dealing with children and adolescents in GUM clinics in the UK are lacking. This needs to be rectified urgently. This survey identifies that further training in the field of child sexual abuse and adolescent sexual health would be welcomed by the respondents.
Adolescent↗
Primary total hip replacement: variations in patient management in Oxford & Anglia, Trent, Yorkshire & Northern 'regions'.
OBJECTIVES: To examine national practice, and variations in practice, concerning total hip replacement; in particular the choice of prosthesis and the involvement of consultants in NHS operations. DESIGN: Pre-operative survey of patients undergoing total hip replacement. SETTING: Five English regions serving combined population of 16.8 million people. SUBJECTS: 13,343 total hip replacement operations in one year commencing September 1996, either in NHS or private sector. MAIN OUTCOME MEASURES: Prosthesis used for surgery, status of surgeons involved in operation, use of laminar flow operating theatre. RESULTS: Prostheses without well documented 5-year survival were used in 5504 (58%) of 9417 operations for which information was available. The consultant was the operator in 4810 (64%) of 7499 NHS operations. In 1352 trainee-led operations, the consultant was present for only 637 (47%); this figure was 54% for trainees in years 1-4 of their training. Substantial variation between NHS consultant firms occurred both for use of prostheses with well documented survival data, and supervision of trainees by the consultant. CONCLUSIONS: This large study is the first attempt to describe national practice for primary total hip replacement. Substantial variation among consultant firms was observed for all indices of practice reported.
Adult↗
Activation of Cdk2 is a requirement for antigen-mediated thymic negative selection.
Apoptosis plays a critical role in T cell development and thymic selection. Thymocytes which undergo antigen-induced negative selection have been demonstrated to die by apoptosis. Despite this, relatively little is known about the specific apoptotic pathway involved in negative selection. We have examined the role of cyclin-dependent kinase 2 (Cdk2), a key regulator of thymocyte apoptosis, in this process. Stimulation of thymocytes with cognate antigen leads to a large increase in Cdk2 kinase activity. We also show that pharmacological inhibitors of Cdk2 block thymocyte apoptosis in response to antigen. Our data show that Cdk2 activity is essential for the apoptotic pathway used in negative selection.
Animals↗
In situ distribution of hepatitis C virus replicative-intermediate RNA in hepatic tissue and its correlation with liver disease.
Liver failure from chronic hepatitis C is the leading indication for liver transplantation in the United States. However, the pathogenesis of liver injury resulting from chronic hepatitis C virus (HCV) infection is not well understood. To examine the relationship between HCV replication in liver tissue and hepatocellular injury, a strand-specific in situ hybridization procedure was developed. The sensitivity and specificity of digoxigenin-labeled riboprobes were optimized by analyzing Northern blots and cell lines expressing HCV RNAs. For the current study, both genomic (sense) and replicative-intermediate (antisense) HCV RNAs were detected and quantified in 8 of 8 liver tissue specimens from infected patients versus 0 of 11 liver tissue specimens from noninfected controls. The distribution pattern for HCV replicative-intermediate RNA in liver was different from that for HCV genomic RNA. HCV genomic RNA was variably distributed throughout infected livers and was located primarily in the cytoplasm of hepatocytes, with some signal in fibroblasts and/or macrophages in the surrounding fibroconnective tissue. However, HCV replicative-intermediate RNA showed a more focal pattern of distribution and was exclusively localized in the cytoplasm of hepatocytes. There was no significant relationship between the distribution pattern for HCV genomic RNA and any indices of hepatocellular injury. However, a highly significant correlation was observed between the percentage of cells staining positive for replicative-intermediate RNA and the degree of hepatic inflammatory activity (P, < 0.0001). Furthermore, the ratio of cells staining positive for HCV replicative-intermediate versus genomic RNA correlated with the histological severity of liver injury (P, 0. 0065), supporting the hypothesis that active replication of HCV in liver tissue may be a significant determinant of hepatocellular injury.
5' Untranslated Regions↗
The value of short and simple measures to assess outcomes for patients of total hip replacement surgery.
OBJECTIVES: To evaluate the performance of a patient assessed outcome measure, the Oxford Hip Score, in a national study of primary hip replacement surgery. DESIGN: A survey of patients' health status before undergoing primary hip replacement surgery and three months and one year after surgery. SETTING: 143 hospitals in three NHS English regions. PATIENTS: 7151 patients admitted for primary total hip replacement surgery over a period of 13 months from September 1996. MAIN MEASURES: For patients, Oxford Hip Score and satisfaction with hip replacement and, for surgeons, American Anesthesiologists' Society (ASA) classification of physical status. RESULTS: The response rates to the postal questionnaire at three and 12 months follow up were 85.2% and 80.7%, respectively. Including all three administrations of the questionnaire, all except two items of the Oxford Hip Score were completed by 97% or more respondents and only one item at one administration appeared marginally to reduce the reliability of the score. The effect sizes for changes in the score from baseline to three months was 2.50 and to 12 months was 3.05. Patients rated by surgeons as being healthy preoperatively by the ASA classification were somewhat more likely to return a completed questionnaire at three months (79.4% versus 75.3%) and 12 months (72.4% versus 70.3%) than those rated as having poorer health. CONCLUSIONS: Overall there was little evidence of difficulties for patients in completing the Oxford Hip Score or of unreliable data, except in relation to one questionnaire item. The instrument was very responsive to change over time and score changes for the Oxford Hip Score related well to patients' satisfaction with their surgery. The instrument is an appropriate measure in terms of validity, responsiveness, and feasibility for evaluating total hip replacement from the
Aged↗
Th cells and Th2 responses can develop in the absence of MHC class II-CD4 interactions.
In this paper, we address the question whether CD4 and MHC class II expression are necessary for the development of the T helper lineage during thymocyte maturation and for activation-induced Th2 responses. To bypass the CD4-MHC class II interaction requirements for positive selection and activation, we used mice that are doubly transgenic for CD8 and for the MHC class I-restricted TCR F5. This transgene combination leads to MHC class I-dependent maturation of CD4 lineage cells. Upon activation, these CD4 lineage T cells secrete IL-4 and give help to B cells but show no cytotoxic activity. Remarkably, neither MHC class II nor CD4 expression are necessary for the generation and helper functions of these cells. This suggests that under normal conditions, coreceptor-MHC interactions are necessary to ensure the canonical combinations of coreceptor and function in developing thymocytes, but that they do not determine functional commitment. Our results also imply that expression of the CD4 gene does not influence, but is merely associated with the decision to establish the T helper program. In addition, we show that activation through TCR-MHC class I interactions can induce Th2 responses independently of CD4 and MHC class II expression.
Animals↗
Bad can act as a key regulator of T cell apoptosis and T cell development.
Bad is a distant relative of Bcl-2 and acts to promote cell death. Here, we show that Bad expression levels are greatly increased in thymocytes during apoptosis. We generated bad transgenic mice to study the action of upregulated Bad expression on T cell apoptosis. The T cells from these mice are highly sensitive to apoptotic stimuli, including anti-CD95. The numbers of T cells are greatly depleted and the processes of T cell development and selection are perturbed. We show that the proapoptotic function of Bad in primary T cells is regulated by Akt kinase and that Bad overexpression enhances both cell cycle progression and interleukin 2 production after T cell activation. These data suggest that Bad can act as a key regulator of T cell apoptosis and that this is a consequence of its upregulation after exposure to death stimuli.
Animals↗
Tramadol or fentanyl analgesia for ambulatory knee arthroscopy.
In a double-blind, randomized, controlled study, 61 patients who received a standardized anaesthetic for day case arthroscopic knee surgery were studied. Group T (n = 31) received tramadol 1.5 mg kg-1, and group F (n = 30) received fentanyl 1.5 micrograms kg-1 at the induction of anaesthesia. All patients also received 20 mL of intra-articular bupivacaine 0.5% at the end of surgery. Assessments were made of pain at rest and on movement, analgesic requirements and side-effects at hourly intervals up to 6 h and by means of a postal questionnaire at 24 h and 48 h post-operatively. Group F had higher pain scores than group T at 4 h only [VAS 3.3 (1.6-5.5) vs. 2.4 (1-4), P = 0.039, respectively; median (interquartile range)]. There were no other significant differences between the groups in terms of pain scores, supplemental analgesic requirements or incidence of side-effects. We conclude that tramadol offers little benefit clinically compared with fentanyl when used at induction of anaesthesia for day case arthroscopic knee surgery. Further studies are indicated in patients with more severe pain to determine the role of tramadol in post-operative analgesia.
Adolescent↗
Signaling in primary thymocytes after presentation of altered peptide ligands by antigen-presenting cells or MHC-peptide tetramers.
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Amino Acid Sequence↗
Vaccinia virus WR gene A5L is required for morphogenesis of mature virions.
The vaccinia virus WR A5L open reading frame (corresponding to open reading frame A4L in vaccinia virus Copenhagen) encodes an immunodominant late protein found in the core of the vaccinia virion. To investigate the role of this protein in vaccinia virus replication, we have constructed a recombinant virus, vA5Li, in which the endogenous gene has been deleted and an inducible copy of the A5 gene dependent on isopropyl-beta-D-thiogalactopyranoside (IPTG) for expression has been inserted into the genome. In the absence of inducer, the yield of infectious virus was dramatically reduced. However, DNA synthesis and processing, viral protein expression (except for A5), and early stages in virion formation were indistinguishable from the analogous steps in a normal infection. Electron microscopy revealed that the major vaccinia virus structural form present in cells infected with vA5Li in the absence of inducer was immature virions. Viral particles were purified from vA5Li-infected cells in the presence and absence of inducer. Both particles contained viral DNA and the full complement of viral proteins, except for A5, which was missing from particles prepared in the absence of inducer. The particles prepared in the presence of IPTG were more infectious than those prepared in its absence. The A5 protein appears to be required for the immature virion to form the brick-shaped intracellular mature virion.
Cell Line↗
The action of Bax and bcl-2 on T cell selection.
T cell development and selection in the thymus are shaped by the induction of apoptosis. However, a direct role in T cell development and selection for any of the molecules known to regulate apoptosis has remained controversial. We have studied the effect of bax and bcl-2 transgenes in recombination activation gene 1-deficient (RAG-1(-/-)) mice transgenic for the major histocompatibility complex class I-restricted F5 T cell receptor. Overexpression of a bax transgene in the thymus seriously impairs the production of mature T cells, whereas bcl-2 overexpression greatly promotes it. The effect of bax and bcl-2 overexpression on antigen-induced negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2 strongly inhibits negative selection, whereas Bax does not affect it. Our data directly show that Bcl-2 family members have specific roles in T cell selection and also lend support to the hypothesis that Bax and Bcl-2 can antagonize each other's action in a certain apoptosis pathway while in another they can be functionally nonreciprocal.
Animals↗