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Biomedical subjects

I Kwan

Publications and source records attributed to I Kwan.

At least 19 recordsLinked to original sources
PubMed2006

Interventions for increasing pedestrian and cyclist visibility for the prevention of death and injuries.

BACKGROUND: Pedestrians and cyclists account for nearly one in three of all road users killed and seriously injured in road traffic crashes. Late detection of other road users is one of the basic driver failures responsible for collisions. Aids to improve pedestrians and cyclist visibility have been used to avert potential collisions. However, the impact of these strategies on drivers' responses, and on pedestrian and cyclist safety is not known. OBJECTIVES: 1. To quantify the effect of visibility aids versus no visibility aids, and of different visibility aids on the occurrence of pedestrian and cyclist-motor vehicle collisions and injuries. 2. To quantify the effect of visibility aids versus no visibility aids, and of different visibility aids on drivers' detection and recognition responses. SEARCH STRATEGY: We searched the CENTRAL, the Cochrane Injuries Group specialised register, MEDLINE, TRANSPORT, National Research Register, PsycInfo and PsycLit. We searched the reference lists of included trials, contacted authors and searched the websites of relevant transport research organisations. The searches were last updated in April 2005. SELECTION CRITERIA: 1. Randomised controlled trials and controlled before-and-after studies of the effect of visibility aids on the occurrence of pedestrian and cyclist-motor collisions and injuries. 2. Randomised controlled trials of the effect of visibility aids on drivers' detection and recognition responses. This included trials where the order of presentation of visibility aids was randomised or balanced using a Latin square design. DATA COLLECTION AND ANALYSIS: Two authors independently screened records, extracted data and assessed trial quality. MAIN RESULTS: We found no trials assessing the effect of visibility aids on pedestrian and cyclist-motor vehicle collisions and injuries. We identified 39 trials assessing the effect of visibility aids on drivers' responses. Fluorescent materials in yellow, red and orange colours improve detection and recognition in the daytime. For night-time visibility, lamps, flashing lights and retroreflective materials in red and yellow colours increase detection and recognition. Retroreflective materials arranged in a 'biomotion' configuration also enhance recognition. Substantial heterogeneity between and within the trials limited the possibility for meta-analysis. Summary statistics and descriptive summaries of the outcomes were presented for individual trials when appropriate. AUTHORS' CONCLUSIONS: Visibility aids have the potential to increase visibility and enable drivers to detect pedestrians and cyclists earlier. Public acceptability of these strategies would merit further development. However, the effect of visibility aids on pedestrian and cyclist safety remains unknown. Studies which collect data on simple, meaningful outcomes are required.

Accidents, Traffic↗
PubMed2005

Conscious sedation and analgesia for oocyte retrieval during in vitro fertilisation procedures.

BACKGROUND: Various methods of sedation and analgesia have been used for pain relief during oocyte recovery in IVF/ICSI procedures. The choice of agents has also been influenced by quality of analgesia as well as by concern about possible detrimental effects on reproductive outcome. OBJECTIVES: To assess the efficacy of conscious sedation and analgesia versus alternative methods on pregnancy outcomes and pain relief in patients undergoing transvaginal oocyte retrieval. SEARCH STRATEGY: We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, The Central Register of Controlled Trials (CENTRAL) , MEDLINE (1966 to present), EMBASE (1980 to present), CINAHL (1982 to present), the National Research Register, and Current Controlled Trials. There was no language restriction. All references in the identified trials and background papers were checked and authors contacted to identify relevant published and unpublished data. SELECTION CRITERIA: Only randomised controlled trials comparing conscious sedation and analgesia versus alternative methods for pain relief during oocyte recovery were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently scanned abstracts of the reports identified by electronic searching to identify relevant papers, extracted data and assessed trial quality. Interventions were classified and analysed under broad categories/strategies of pain relief comparing conscious sedation/analgesia with alternative methods and administration protocols. MAIN RESULTS: Our search strategy identified 390 potentially eligible reports and 12 papers met our inclusion criteria. There were no significant differences in clinical pregnancy rates per woman and patient satisfaction between the methods compared. Women's perception of pain showed conflicting results. Due to considerable heterogeneity, in terms of types and dosages of sedation or analgesia used, and tools used to assess the principal outcomes of pain and satisfaction, a meta-analysis of all the studies was not attempted. Of the three trials which compared the effect of conventional medical analgesia plus paracervical block versus electro-acupuncture plus paracervical block, there was no significant difference in clinical pregnancy rates per woman in the two groups (OR 1.01; 95% CI 0.73 to 1.4). For intra-operative pain score as measured by visual analogue scale (VAS), there was a significant difference (WMD -4.95; 95% CI -7.84 to -2.07), favouring conventional medical analgesia plus paracervical block . There was also a significant difference in intra-operative pain by VAS between patient-controlled sedation and physician-administered sedation (WMD 5.98; 95% CI 1.63 to 10.33), favouring physician -administered sedation. However, as different types and dosages of sedative and analgesic agents were used in these trials, these data should be interpreted with caution. For the rest of the trials, a descriptive summary of the outcomes was presented. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effect of different methods of pain relief when compared with conscious sedation and analgesia used during oocyte recovery. In this review, no one particular pain relief method or delivery system appeared to be better than the other. In future, greater consensus is needed to determine both the tools used to evaluate pain and the timing of pain evaluation during and after the procedure. Pain assessment using both subjective and objective measures may merit consideration. In addition, future trials should include intra- and post-operative adverse respiratory and cardiovascular events as outcomes.

Analgesia↗
PubMed2003

How can a nurse intervention help people with newly diagnosed epilepsy? A qualitative study of patients' views.

The aim was to describe the patients' views of the challenges posed by a new diagnosis of epilepsy and their assessment of a nurse intervention. Neurologists in South-East England referred patients into the study. Following a trial of a nurse intervention a subgroup of patients were purposefully identified for in depth interviews. Transcriptions of tape-recorded interviews were analysed using qualitative methodology. We found that younger people with epilepsy seemed to experience more trouble with driving, jobs and managing their lives in the context of new epilepsy, while older people saw epilepsy as just another illness to cope with. Patients reported difficulty in remembering what their doctors told them which they attributed partly to lack of time available in the consultation. They valued the time, and the technique of probing with explanations used by the nurse. The nurse intervention was seen as useful in making sense of symptoms, tests, risk management, and driving regulations and in helping manage their medicine taking. We conclude that people with newly diagnosed epilepsy face different challenges, some of which are related to their age at diagnosis. Patients reported help from the nurse with understanding the diagnosis, tests, risk management and taking their medication. Follow-up is necessary to measure behavioural effects on self-management in the long-run.

Adolescent↗
PubMed2002

Interventions for increasing pedestrian and cyclist visibility for the prevention of death and injuries.

BACKGROUND: Pedestrians and cyclists account for nearly one in three of all road users killed and seriously injured in road traffic crashes. Late detection of other road users is one of the basic driver failures responsible for collisions. Aids to improve pedestrians and cyclist visibility have been used to avert potential collisions. However, the impact of these strategies on drivers' responses, and on pedestrian and cyclist safety is not known. OBJECTIVES: 1. To quantify the effect of visibility aids vs no visibility aids, and of different visibility aids on the occurrence of pedestrian and cyclist-motor vehicle collisions and injuries. 2. To quantify the effect of visibility aids vs no visibility aids, and of different visibility aids on drivers' detection and recognition responses. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the Injuries Group Specialised Register, MEDLINE, TRANSPORT, TRANSDOC from ECMT (European Conference of Ministers of Transport), IRRD (International Road Research Documentation), TRIS (Transportation Research Information Services), NRR (National Research Register), PsycInfo and PsycLit. SELECTION CRITERIA: 1. Randomised controlled trials and controlled before/after trials of the effect of visibility aids on the occurrence of pedestrian and cyclist-motor collisions and injuries. 2. Randomised controlled trials of the effect of visibility aids on drivers' detection and recognition responses. This included trials where the order of presentation of visibility aids was randomised or balanced using a Latin square design. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened records, extracted data and assessed trial quality. MAIN RESULTS: We found no trials assessing the effect of visibility aids on the occurrence of pedestrian and cyclist-motor vehicle collisions and injuries. We identified 37 trials assessing the effect of visibility aids on drivers' responses. Fluorescent materials in yellow, red and orange colours improve detection and recognition in the daytime. For night-time visibility, lamps, flashing lights and retroreflective materials in red and yellow colours increase detection and recognition. Retroreflective materials arranged in a 'biomotion' configuration also enhance recognition. Substantial heterogeneity between and within the trials limited the possibility for meta-analysis. Summary statistics and descriptive summaries of the outcomes were presented for individual trials when appropriate. REVIEWER'S CONCLUSIONS: Visibility aids have the potential to increase visibility and enable drivers to detect pedestrians and cyclists earlier. Public acceptability of these strategies would merit further development. However, the effect of visibility aids on pedestrian and cyclist safety remains unknown. Studies which collect data on simple, meaningful outcomes are required.

Accidents, Traffic↗
PubMed2002

How can a nurse intervention help people with newly diagnosed epilepsy? A qualitative study (of patients' views).

The aim was to describe the patients' views of the challenges posed by a new diagnosis of epilepsy and their assessment of a nurse intervention. Neurologists in South-East England referred patients into the study. Following a trial of a nurse intervention a subgroup of patients were purposefully identified for in-depth interviews. Transcriptions of tape-recorded interviews were analysed using qualitative methodology. We found that younger people with epilepsy seemed to experience more trouble with driving, jobs and managing their lives in the context of new epilepsy, while older people saw epilepsy as just another illness to cope with. Patients reported difficulty in remembering what their doctors told them which they attributed partly to lack of time available in the consultation. They valued the time, and the technique of probing with explanations used by the nurse. The nurse intervention was seen as useful in making sense of symptoms, tests, risk management, and driving regulations and in helping manage their medicine taking. We conclude that people with newly diagnosed epilepsy face different challenges, some of which are related to their age at diagnosis. Patients reported help from the nurse with understanding the diagnosis, tests, risk management and taking their medication. Follow-up is necessary to measure behavioural effects on self-management in the long run.

Adolescent↗
PubMed2001

Timing and volume of fluid administration for patients with bleeding following trauma.

BACKGROUND: Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding. OBJECTIVES: To assess the effects of early versus delayed, and larger versus smaller volume of fluid administration in trauma patients with bleeding. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the specialised register of the Injuries Group, MEDLINE, EMBASE, the National Research Register and the Science Citation Index. We checked reference lists of identified articles and contacted authors and experts in the field. SELECTION CRITERIA: Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration: Three trials reported mortality and two coagulation data. In the first trial (n=598) relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval of 1.00-1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9-4.5) and 4.3 (95% CI 1.74-6.9) seconds respectively. In the second trial (n=50) RR for death with early blood transfusion was 5.4 (95% CI 0.3-107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0-8.0) seconds. In the third trial (n=1309) RR for death with early fluid administration was 1.06 (95% CI 0.77-1.47). Larger versus smaller volume of fluid administration: Three trials reported mortality and one coagulation data. In the first trial (n=36) RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28-22.29). Prothrombin time and Partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n=99) RR for death with a high (100 mm Hg) compared to low (70 mm Hg) systolic blood pressure resuscitation target was 1.02 (95% CI 0.27-3.85). In the third trial (n=25) there were no deaths. REVIEWER'S CONCLUSIONS: We found no evidence from randomised controlled trials to support early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.

Hemorrhage↗
PubMed2001

Spinal immobilisation for trauma patients.

BACKGROUND: Spinal immobilisation involves the use of a number of devices and strategies to stabilise the spinal column after injury and thus prevent spinal cord damage. The practice is widely recommended and widely used in trauma patients with suspected spinal cord injury in the pre-hospital setting. OBJECTIVES: To quantify the effect of different methods of spinal immobilisation (including immobilisation versus no immobilisation) on mortality, neurological disability, spinal stability and adverse effects in trauma patients. SEARCH STRATEGY: We searched the Cochrane Controlled Trial Register (CCTR), the specialised register of the Cochrane Injuries Group, MEDLINE, EMBASE, CINAHL, PubMed and the National Research Register. We checked reference lists of all articles and contacted experts in the field to identify eligible trials. Manufacturers of spinal immobilisation devices were also contacted for information. SELECTION CRITERIA: Randomised controlled trials comparing spinal immobilisation strategies in trauma patients with suspected spinal cord injury. Trials in healthy volunteers were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria to trial reports and extracted data. MAIN RESULTS: We found no randomised controlled trials of spinal immobilisation strategies in trauma patients. REVIEWER'S CONCLUSIONS: We did not find any randomised controlled trials that met the inclusion criteria. The effect of spinal immobilisation on mortality, neurological injury, spinal stability and adverse effects in trauma patients remains uncertain. Because airway obstruction is a major cause of preventable death in trauma patients, and spinal immobilisation, particularly of the cervical spine, can contribute to airway compromise, the possibility that immobilisation may increase mortality and morbidity cannot be excluded. Large prospective studies are needed to validate the decision criteria for spinal immobilisation in trauma patients with high risk of spinal injury. Randomised controlled trials in trauma patients are required to establish the relative effectiveness of alternative strategies for spinal immobilisation.

Humans↗
PubMed2001

Advanced trauma life support training for ambulance crews.

BACKGROUND: There is an increasing global burden of disease from injuries. Models of trauma care initially developed in high-income countries are also being adopted in low and middle-income countries (LMIC). Amongst these ambulance crews with Advanced Life Support (ALS) training are being promoted in LMIC as a strategy for improving outcomes for victims of trauma. However there is controversy as to the effectiveness of this health service intervention, and the evidence has yet to be rigorously appraised. OBJECTIVES: To quantify the effectiveness of ambulance crews with ALS training versus crews with any other level of training in reducing mortality and morbidity in trauma patients. SEARCH STRATEGY: We searched the Cochrane Controlled Trial Register (CCTR), the specialised register of the Cochrane Injuries Group, MEDLINE, EMBASE, CINAHL, PubMed and the National Research Register. We checked references of background papers and contacted authors to identify additional published or unpublished data. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials and controlled before-and-after studies comparing effectiveness of ambulance crews with ALS training versus crews with any other levels of training in reducing mortality and morbidity in trauma patients. Studies which compared crews staffed by physicians versus others were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied eligibility criteria to trial reports for inclusion and extracted data. MAIN RESULTS: We found one randomised controlled trial, which included 16 trauma cases. However, outcome data were added to the main non-randomised cohort in the analysis, and data on these 16 cases are not yet available. REVIEWER'S CONCLUSIONS: In the absence of evidence of the effectiveness of advanced life support, strong argument could be made that it should not be promoted outside the context of a properly concealed and otherwise rigorously conducted randomised controlled trial.

Controlled Clinical Trials as Topic↗
PubMed2000

An epilepsy care package: the nurse specialist's role.

Deficiencies in existing primary care for people with epilepsy are well-recognized in the United Kingdom and include a lack of structure and an inability to meet the patients' needs for information and support to cope with their epilepsy. The introduction of clinics set up by nurse specialists within family practice in a few United Kingdom cities has met with a high degree of acceptability and satisfaction from patients. A package of care was developed to support epilepsy management in the community in the United Kingdom. It includes provision of advice and information, counseling, and interdisciplinary liaison. Nurse specialists with a sound training in epilepsy can adopt a proactive role and effectively deliver this package.

Adult↗
PubMed2000

Newly diagnosed epilepsy: can nurse specialists help? A randomized controlled trial. Epilepsy Care Evaluation Group.

PURPOSE: To describe a group of people with newly diagnosed epilepsy and to test the effect of an epilepsy nurse specialist on patients' knowledge of epilepsy, satisfaction with the advice provided, and psychological well-being. METHODS: Neurologists in the United Kingdom (U.K.) recruited adults with newly diagnosed epilepsy. Patients were randomized to receive the offer of two appointments with an epilepsy nurse specialist or usual medical care. The main outcome measures were a questionnaire assessing patients' knowledge of epilepsy, the Hospital Anxiety and Depression Scale, and patients' reported satisfaction with the advice and explanations provided on key epilepsy-related topics. RESULTS: Ninety people with new epilepsy completed the trial. At baseline, fewer than half the patients reported having been given enough advice on epilepsy, and there were important differences in patients' knowledge of epilepsy. Lack of a U.K. school-leaving examination pass (General Certificate School Examination) was associated with lower knowledge of epilepsy (p = 0.03). At follow-up, the patients randomized to see the nurse specialist were significantly more likely to report that enough advice had been provided on most epilepsy-related topics compared with the control group. There were no significant differences in knowledge of epilepsy scores. However, there were significant differences in the group who, at baseline, had knowledge scores in the lowest quartile; those randomized to the nurse had higher knowledge scores (42.7 vs. 37.2; p < 0.01). Compared with doctors, the nurse was highly rated for providing clear explanations. CONCLUSIONS: Patients who have less general education have less knowledge of epilepsy. The introduction of a nurse specialist in epilepsy is associated with a significant increase in patient reports that enough advice has been provided. Nurse intervention appears to help those with the least knowledge of epilepsy improve their knowledge scores.

Adolescent↗
PubMed1999

The effect of a special nurse on patients' knowledge of epilepsy and their emotional state. Epilepsy Evaluation Care Group.

BACKGROUND: People with epilepsy often report being given insufficient information and support. However, there is little evidence from general practice about how much they know and how they feel. AIM: To describe social differences in the knowledge of epilepsy of people with the condition and test the potential effect of a nurse intervention in general practice on patients' knowledge and depression levels. METHOD: A questionnaire that included measures of knowledge, anxiety, and depression was sent to people with epilepsy aged over 15 years who were registered with 37 general practitioners. Responders were randomized to a controlled trial, offering either two appointments with an epilepsy nurse or usual care. Six months later they were reassessed. RESULTS: Two hundred and fifty-one out of 283 (89%) of the patients with epilepsy completed questionnaires and entered the study at Stage 1. One hundred and ninety-six out of 232 (84%) of those who entered the study, who remained in the practices and were eligible, returned questionnaires at Stage 2. The average duration of epilepsy was 23 years (range 2-79 years). There were significant differences in patients' levels of knowledge of epilepsy at Stage 1. Younger people, those who had left school after 16 years of age, those with GCSEs, and people who belonged to self-help groups had higher knowledge levels, and these were independent effects. Older people and those with a recent epilepsy attack had significantly higher depression scores. Knowledge scores did not differ significantly after the nurse intervention (Stage 2). At Stage 2, the risk of depression was less in the group randomized to be offered nurse input; the effect was mainly in a subgroup of patients with no recent epilepsy attack; their risk of depression was a third of the risk in the control group. CONCLUSIONS: Knowledge of epilepsy differs significantly, with social factors and self-help group membership having independent effects. A nurse-run clinic reduced the risk of depression for people with no recent epilepsy attack, but knowledge levels were not affected. This does not exclude the potential for patients learning more about epilepsy; it may be useful to suggest that patients join self-help groups early on.

Adolescent↗
PubMed1996

Steroidogenic properties of a spontaneously established porcine granulosa cell line (PGC-2).

A spontaneously established porcine granulosa cell line (PGC-2) was cloned through the continuous culturing of primary granulosa cells collected from equine chorionic gonadotropin (eCG)-treated prepubertal gilts. This established cell line has undergone approximately 100 passages and shows contact-inhibition of growth. PGC-2 stained with a monoclonal antibody (mAb) directed against cytokeratin, indicating its epithelial nature, but not with a mAb directed against vimentin, suggesting that it is not fibroblast-derived. Immunoblotting revealed that PGC-2 expresses cadherin, an epithelial Ca+2-dependent cell adhesion molecule. The cells were dependent on serum for growth and had a doubling time of approximately 20 hr when cultured with 10% fetal bovine serum. The cell line was examined for the presence of FSH receptors, cAMP responses, and steroidogenic capabilities. The cell line lacks FSH receptors as assessed by radiolabelled-ligand binding, and no transcripts for FSH receptor were detected by Northern blotting of total cellular RNA. Neither FSH nor cholera toxin (0.5 ng/mL) stimulated increases in cAMP levels in these cells, whereas forskolin (10 microM) induced a fivefold increase in cAMP production. When a higher concentration of cholera toxin (300 ng/mL) was used, however, cAMP levels doubled by 2 hr. Despite a lack of responsiveness to purified of SH or oLH, the cells were capable of progesterone and estradiol production when provided with the appropriate substrates. We conclude that PGC-2 display properties that are similar to immature granulosa cells and may provide a suitable in vitro model for the study of granulosa cell function.

Animals↗
PubMed1994

Viral induction of the human beta interferon promoter: modulation of transcription by NF-kappa B/rel proteins and interferon regulatory factors.

Multiple regulatory domains within the -100 region of the beta interferon (IFN-beta) promoter control the inducible response of the IFN gene to virus infection. In this study, we demonstrate that the formation of NF-kappa B-specific complexes on the positive regulatory domain II (PRDII) precedes the onset of detectable IFN-beta transcription in Sendai virus-infected cells. By using NF-kappa B subunit-specific antibodies, a temporal shift in the composition of NF-kappa B subunits in association with the PRDII domain is detected as a function of time after virus infection. Furthermore, a virus-induced degradation of I kappa B alpha (MAD3) protein is observed between 2 and 8 h after infection; at later times, de novo synthesis of I kappa B alpha restores I kappa B alpha to levels found in uninduced cells and correlates with the down regulation of IFN-beta transcription. In cotransfection experiments using various NF-kappa B subunit expression plasmids and two copies of PRDII/NF-kappa B linked to a chloramphenicol acetyltransferase reporter gene, we demonstrate that expression of p65, c-Rel, or p50 or combinations of p50-p65 and p65-c-Rel differentially stimulated PRDII-dependent transcription. Coexpression of I kappa B alpha completely abrogated p65-, c-Rel-, or p65-p50-induced gene activity. When the entire IFN-beta promoter (-281 to +19) was used in coexpression studies, synergistic stimulation of IFN-beta promoter activity was obtained when NF-kappa B subunits were coexpressed together with the IFN regulatory factor 1 (IRF-1) transcription factor. Overexpression of either I kappa B or the IRF-2 repressor was able to abrogate inducibility of the IFN-beta promoter. Thus, multiple regulatory events--including differential activation of DNA-binding NF-kappa B heterodimers, degradation of I kappa B alpha, synergistic interaction between IRF-1 and NF-kappa B, and decreased repression by I kappa B and IRF-2--are all required for the transcriptional activation of the IFN-beta promoter.

Animals↗
PubMed1994

Disruption of I kappa B alpha regulation by antisense RNA expression leads to malignant transformation.

NF-kappa B transcription factors regulate the expression of a variety of genes involved in immune regulation and cell growth. In most cell types NF-kappa B proteins are localized in an inactive form in the cytoplasm coupled to the inhibitory I kappa B proteins. Viruses, cytokines, lipopolysaccharides and other stimulating agents promote the dissociation of the cytosolic NF-kappa B/I kappa B complexes, via phosphorylation and degradation of I kappa B, resulting in the translocation of DNA binding, NF-kappa B complexes to the nucleus. To further understand the association of I kappa B with cell growth regulation, the effect of ectopic expression of sense and antisense I kappa B genes was examined in NIH3T3 cells. Overexpression of I kappa B alpha antisense RNA but not I kappa B gamma antisense RNA decreased the steady state levels of I kappa B alpha protein, altered NF-kappa B DNA binding and gene activity and, most importantly, induced malignant transformation as measured by saturation density, growth in soft agar and tumorigenicity in nude mice. In contrast, overexpression of I kappa B alpha resulted in decreased saturation density, a flattened cellular morphology and decreased NF-kappa B dependent reporter gene activity. These results indicate that overexpression of an I kappa B alpha antisense RNA may disrupt the NF-kappa B/I kappa B autoregulatory loop, leading to cellular transformation. Our results raise the interesting possibility that I kappa B alpha represents a potential tumor suppressor activity.

3T3 Cells↗
PubMed1993

Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.

The -300 region of the interleukin 1 beta (IL-1 beta) promoter contains a functional NF-kappa B binding site composed of the decamer sequence 5'-GGGAAAATCC-3'. Probes representing the -300 region or the NF-kappa B site alone interacted with NF-kappa B proteins present in phorbol myristate acetate-, lipopolysaccharide-, or Sendai virus-induced myeloid cell extracts as well as recombinant NFKB1 (p50) and RelA (p65); furthermore, NF-kappa B protein-DNA complex formation was dissociated in vitro by the addition of recombinant I kappa B alpha. Mutation of the NF-kappa B site in the context of the IL-1 beta promoter reduced the responsiveness of the IL-1 beta promoter to various inducers, including phorbol ester, Sendai virus, poly(rI-rC), and IL-1 beta. A 4.4-kb IL-1 beta promoter fragment linked to a chloramphenicol acetyltransferase reporter gene was also preferentially inducible by coexpression of individual NF-kappa B subunits compared with a mutated IL-1 beta promoter fragment. When multiple copies of the IL-1 beta NF-kappa B site were linked to an enhancerless simian virus 40 promoter, this element was able to mediate phorbol ester- or lipopolysaccharide-inducible gene expression. In cotransfection experiments, RelA (p65) and c-Rel (p85) were identified as the main subunits responsible for the activation of the IL-1 beta NF-kappa B site; also, combinations of NFKB1 (p50) and RelA (p65) or c-Rel and RelA were strong transcriptional activators of reporter gene activity. The presence of a functional NF-kappa B binding site in the IL-1 beta promoter suggests that IL-1 positively autoregulates its own synthesis, since IL-1 is a strong inducer of NF-kappa B binding activity. Thus, the IL-1 beta gene may be considered as an important additional member of the family of cytokine genes regulated in part by the NF-kappa B/rel family of transcription factors.

Base Sequence↗
PubMed1978

Nonhomogeneous excitatory synapses of a crab stomach muscle.

Neuromuscular synapses of pyloric muscle P1 in the blue crab Callinectes sapidus were examined using electrophysiological and electron microscopic methods. The muscle is innervated by a single excitatory axon of the stomatogastric ganglion. Excitatory postsynaptic potentials show striking facilitation at very low frequencies of stimulation, indicating very slow decay of the facilitation process after a single nerve impulse. Quantal content of transmitter release at a low frequency of stimulation averaged 1.5. Evidence was obtained that not all synapses on a muscle fiber are equivalent. This was particularly evident at the morphological level in serially sectioned nerve terminals. On each nerve terminal examined, a wide range of synapse sizes was found. Synaptic contact areas ranged from less than 0.5 micron2 to almost 10 micron2; the latter value is large compared with those obtained for other crustacean neuromuscular synapses. Most of the smaller synapses lacked the presynaptic dense bodies which are putative release sites for the transmitter substance. The larger synapses all had presynaptic dense bodies, and some showed evidence of splitting apart into smaller subunits. It is postulated that about half the morphologically identified synapses are relatively inactive.

Animals↗