Cervical screening: what is the point?
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Cause of Death↗
Biomedical subjects
D Campbell
Publications and source records attributed to D Campbell.
The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide.
Anandamide is an endogenous ligand for delta 9-tetrahydrocannabinol (THC) receptors. Incubation of cultured cells with anandamide or THC causes increased arachidonic acid release and eicosanoid biosynthesis. Here we demonstrate that the MAP kinase signal transduction pathway contributes to this response. Treatment of WI-38 fibroblasts with anandamide causes increased MAP kinase activity and increased phosphorylation of the arachidonate-specific cytoplasmic phospholipase A2 (cPLA2). Significantly, MAP kinase phosphorylates and activates cPLA2 [Lin, et al., Cell, 72 (1993) 269-278]. The MAP kinase signal transduction pathway may therefore mediate the effects of anadamide on cPLA2 activation and arachidonic acid release.
Arachidonic Acid↗
Transcription factor ATF2 regulation by the JNK signal transduction pathway.
Treatment of cells with pro-inflammatory cytokines or ultraviolet radiation causes activation of the c-Jun NH2-terminal protein kinase (JNK). Activating transcription factor-2 (ATF2) was found to be a target of the JNK signal transduction pathway. ATF2 was phosphorylated by JNK on two closely spaced threonine residues within the NH2-terminal activation domain. The replacement of these phosphorylation sites with alanine inhibited the transcriptional activity of ATF2. These mutations also inhibited ATF2-stimulated gene expression mediated by the retinoblastoma (Rb) tumor suppressor and the adenovirus early region 1A (E1A) oncoprotein. Furthermore, expression of dominant-negative JNK inhibited ATF2 transcriptional activity. Together, these data demonstrate a role for the JNK signal transduction pathway in transcriptional responses mediated by ATF2.
Activating Transcription Factor 2↗
A functional factor X deficiency.
A functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation.
Adult↗
The influence of abuse on pregnancy intention.
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Battered Women↗
Tissue-specific targeting of cytokine unresponsiveness in transgenic mice.
The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo. Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction. Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development. These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo.
Animals↗
Non-response in a population study after an environmental disaster.
After the grounding of the tanker MV Braer off the coast of Shetland an epidemiological study was rapidly instigated to determine any immediate or long-term health effects on the exposed resident population. The study was carried out in two phases, at the time of the grounding and five months later. The objective of this study is to determine the reasons for non-response in both phases of the Shetland Health Study. A telephone survey was performed on a systematic sample of non-responders from the exposed population in both phases of the study. The setting was the south mainland of Shetland. Fifty-nine of the 215 non-responders in the first phase of the study and 16 of the 86 non-responders in the second phase were surveyed. The main reasons for non-response were attitudinal rather than situational or organisational. Non-responders did not feel their health was affected, were not interested in the study or did not think the study was useful. Some were put off by the biological tests involved and some had difficulties with appointment times. Practical issues such as flexible appointment systems are easier to address than client characteristics but factors relating to distrust and indifference must be addressed if non-response rates are to be minimised.
Case-Control Studies↗
Pseudothrombocytopenia in plateletpheresis donors.
BACKGROUND: EDTA pseudothrombocytopenia (PTCP) is an in vitro artifact in which the anticoagulation of blood with EDTA is associated with in vitro agglutination of platelets, resulting in a spuriously low platelet count. In apheresis donors, whole-blood samples for complete blood counts are routinely drawn into tubes anti-coagulated with EDTA. STUDY DESIGN AND METHODS: Records of apheresis donors were examined to identify persons in whom the postdonation counts were less than 100 x 10(9) per L. Identified donors were studied to confirm the presence of PTCP by drawing blood samples into EDTA, heparin, and trisodium citrate for serial platelet counts at room-temperature incubation. Platelet counts in citrated plasma were measured before and after the addition of EDTA. A single HLA-matched component from an identified PTCP donor was monitored for response by corrected count increment in the recipient. RESULTS: A total of nine donations were identified, involving 2 donors from a population of 945 donors (prevalence 0.2%). On testing, both donors were confirmed to have PTCP. The addition of EDTA to citrated plasma did not affect the platelet count. Response in a recipient to an HLA-matched component showed an acceptable corrected count increment. CONCLUSION: PTCP may occur in plateletpheresis donors and result in needless medical referral or donor deferral. PTCP does not appear to alter the yield content of the component or to be passively transferred to a recipient.
Blood Donors↗
Smoking-related beliefs and behaviour among adults with asthma in a representative population sample.
BACKGROUND: Smoking and exposure to environmental tobacco smoke are inadvisable for adults with asthma. AIMS: To determine the smoking prevalence and daily smoking rate of asthmatics and compare smoking-related beliefs and behaviours among smokers with and without asthma. To compare beliefs of asthmatics about passive smoking and asthma, how many are exposed at home and what they do when they are exposed, with people who do not have asthma. METHODS: A representative population survey of 3019 South Australian adults aged 15 years and older interviewed in their own homes in late 1992. RESULTS: Twenty-eight per cent of asthmatics were smokers; mean daily smoking rate was 17.6. Asthmatics had similar patterns of smoking, readiness to quit and quit attempt histories as people without asthma. More than 40% of smokers with asthma did not perceive that smoking had greatly affected their health, over half did not believe they were at risk in future and two-thirds did not think future health problems would be serious. Among non-smokers, despite being more convinced of the effects of passive smoking on asthma, and being more concerned about exposure, those with asthma were no more likely to take protective action in response to actual or imminent exposure than those without asthma. One in ten non-smokers with asthma were exposed to smoking at home. CONCLUSIONS: The smoking habits of adults with asthma are cause for concern, with many asthmatic smokers perceiving they are not personally at risk from their smoking. Health education principles should be used by health professionals caring for asthmatic smokers to guide the selection and delivery of smoking cessation strategies. Prevailing restrictions on indoor smoking play an important role in protecting the respiratory health of non-smokers with asthma.
Adolescent↗
NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus.
The nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of cytokine genes. Here, we report the cDNA cloning, chromosomal localization, and initial characterization of a transcription factor related to NFATp and NFATc. The novel molecule, designated NFATx, exhibits in its middle a region very similar to the Rel homology domain in NFATc and NFATp. The amino-terminal region of NFATx also shows significant similarities to corresponding sequences in NFATc and NFATp and contains three copies of a conspicuous 17-residue motif of unknown function. We provide evidence showing that NFATx can reconstitute binding to the NFAT-binding site from the interleukin 2 promoter when combined with AP1 (c-Fos/c-Jun) polypeptides and that NFATx is capable of activating transcription of the interleukin 2 promoter in COS-7 cells when stimulated with phorbol ester and calcium ionophore. NFATx mRNA is preferentially and remarkably found in the thymus and at lower levels in peripheral blood leukocytes. The expression pattern of NFATx, together with its functional activity, strongly suggests that NFATx plays a role in the regulation of gene expression in T cells and immature thymocytes.
Amino Acid Sequence↗
The role of the father in a pre-suicide state.
In the self-examination that followed a patient's suicide attempt, the author was worried by three features which he had observed in an earlier suicide attempt by another patient: (1) the father had not featured in the analysis as much as would have been expected, (2) the suicide attempt occurred during a period when the time and place boundaries of the analytic setting were in jeopardy, e.g. the patient was absent from sessions; and (3) this coincided with the author having temporarily underestimated the suicidal risk. These three features were illuminated by a transference to a father who did not claim his child for himself and offer an alternative to fusion with a dangerous mother. Although the patient's suicide fantasies were based on a pathological bond with his mother, during the pre-suicide state the internalised father who had failed to protect his son from mother was evoked in the countertransference to function as a sanction for the suicidal act.
Adult↗
Later effects of grounding of tanker Braer on health in Shetland.
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Adolescent↗
Ligand for FLT3/FLK2 receptor tyrosine kinase regulates growth of haematopoietic stem cells and is encoded by variant RNAs.
The FLT3/FLK2 receptor tyrosine kinase is closely related to two receptors, c-Kit and c-Fms, which function with their respective ligands, Kit ligand and macrophage colony-stimulating factor to control differentiation of haematopoietic and non-haematopoietic cells. FLT3/FLK2 is thought to be present on haematopoietic stem cells and found in brain, placenta and testis. We have purified to homogeneity and partially sequenced a soluble form of the FLT3/FLK2 ligand produced by mouse thymic stromal cells. We isolated several mouse and human complementary DNAs that encode polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble ligand. The purified ligand enhances the response of mouse stem cells and a primitive human progenitor cell population to other growth factors such as interleukins IL-3 and IL-6 and to granulocyte-macrophage colony-stimulating factor, and also stimulates fetal thymocytes.
Amino Acid Sequence↗
Auditory brainstem responses after ovariectomy and estrogen replacement in rat.
Previous work has suggested possible influences of ovarian hormones on evoked potentials in the auditory system. The aim of this project was to study the effects of ovariectomy and subsequent administration of estrogen replacement on the auditory brainstem response and the middle latency response. Groups of 90 day-old Long-Evans hooded rats were anesthetized for bilateral ovariectomies (ovex) and recordings made 3 weeks later. During the week prior to recordings some ovariectomized groups received subcutaneous injections of 10, 100 or 500 micrograms/kg Premarin in peanut oil, and other unoperated animals received vehicle injections. Recordings from vertex/chin using needle electrodes and pure tone stimulus parameters were made under Rompun/Ketamine. The results using 40 kHz tone stimuli showed that mean latencies for ovex animals were longer than animals in the 100 micrograms/kg Premarin group for waves 1a, 1an, 1b, 11, 111, 111n, and 1V/V. Other posthoc comparisons at 40 kHz stimulation revealed differences between control and 100 micrograms/kg Premarin groups for latencies of waves 1b, 1bn, 11 and 111. Latency reduction appeared for waves 1b, 1bn, 11 and 111 for the 10 ovex group, but only at wave 11 for the 500 ovex group, compared to ovex-only animals. Data from 8 kHz stimulation also demonstrated significant differences between the ovex and ovex 100 groups at waves 1bn and Vn. Observations of interpeak latency differences, especially between waves 1a and 11, suggested central as well as cochlear involvement in hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustic Stimulation↗
Hemostatic effects of stress hormone infusion.
BACKGROUND: Surgery causes changes in hemostasis, leading to a hypercoagulable state. This postoperative increase in hemostatic function is attenuated in patients receiving regional anesthesia compared with those receiving general anesthesia. Regional anesthesia also decreases the neuroendocrine response to surgery compared with general anesthesia, and this effect is hypothesized to be responsible for the differences in hemostatis. To test the hypothesis that neuroendocrine hormones cause changes in hemostasis, we infused stress hormones into normal volunteers and measured hemostatic function. METHODS: After drug screening, 12 normal volunteers were studied. On two admissions, volunteers randomly received either stress hormone (epinephrine, cortisol, or glucagon) or placebo infusion for 24 h. During infusion, patients remained at bed rest and received controlled meals. Blood was obtained from indwelling venous catheters before infusion and 2, 8, and 24 h after the start of infusion. Blood was analyzed for neuroendocrine hormone concentrations, glucose, complete blood count, coagulation proteins, platelet reactivity, and activity of the fibrinolytic system. RESULTS: In the stress hormone group, concentrations of epinephrine, norepinephrine, cortisol, glucagon, and insulin were increased during the infusion period compared with those in the placebo group. Glucose concentrations and white blood cell counts were increased in the stress hormone group compared with those in the placebo group. Circulating fibrinogen concentrations increased 30% and ex vivo collagen-induced platelet reactivity increased 123% (aggregation) and 103% (dense granule release) in the stress hormone infusion group, whereas there was no change in the placebo group. Fibrinolytic proteins were similar in both groups, demonstrating a decrease in plasminogen activator inhibitor-1 activity at 8 and 24 h (196% in the hormone group vs. 199% in the placebo group). CONCLUSIONS: Infusion of stress hormones to concentrations found during surgery is safely tolerated and causes metabolic changes observed with surgery. Stress hormone infusion increases ex vivo platelet reactivity and fibrinogen concentrations that resemble changes seen postoperatively but does not recreate the postoperative decrease in fibrinolytic activity. Differences in neuroendocrine response between types of anesthesia may explain some postoperative changes in platelet function and acute phase reactivity, but additional uncharacterized factors are responsible for the differences in fibrinolysis.
Adolescent↗
Nebulised lignocaine: an aid to weaning.
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Administration, Inhalation↗
Age-related changes in beta-adrenergic neuroeffector systems in the human heart.
BACKGROUND: Aging decreases cardiac beta-adrenergic responsiveness in model systems and in humans in vivo. The purpose of this study was to comprehensively evaluate the age-related changes in the beta-receptor-G protein-adenylyl cyclase complex in nonfailing human hearts. METHODS AND RESULTS: Twenty-six nonfailing explanted human hearts aged 1 to 71 years were obtained from organ donors and subjected to pharmacological investigation of beta-adrenergic neuroeffector systems. When the population was subdivided into the 13 youngest and 13 oldest subjects, total beta-receptor density assessed by maximum [125I]ICYP binding (beta max) was reduced in older hearts by 37% in left ventricles and 31% in right ventricles (both P < .05), and the downregulation was confined to the beta 1 subtype (r = .78 left ventricle beta 1 density versus donor age). Older donor hearts exhibited a 3- to 4-fold rightward shift of ICYP-isoproterenol (ISO) competition curves and demonstrated 43% fewer receptors in a high-affinity agonist binding state (P < .05). Older hearts exhibited decreased adenylyl cyclase stimulation by ISO, by zinterol (beta 2-agonist), and by the G protein-sensitive probes forskolin, Gpp(NH)p, and NaF. In contrast, there was no change in response to manganese, a specific activator of the adenylyl cyclase catalytic subunit. Toxin-catalyzed ADP ribosylation in membranes prepared from older versus younger hearts revealed a 29% to 30% reduction (P < .05) with cholera toxin (Gs) but no difference with pertussis toxin (Gi). The systolic contractile response of isolated right ventricular trabeculae to ISO was decreased by 46%, with a 10-fold increase in ISO EC50 in older relative to younger donor hearts. CONCLUSIONS: There is a profound decrease in cardiac beta-adrenergic responsiveness with aging. This occurs by multiple mechanisms including downregulation and decreased agonist binding of beta 1-receptors, uncoupling of beta 2-receptors, and abnormal G protein-mediated signal transduction.
Adenylyl Cyclases↗
Venous embolization after deflation of lower extremity tourniquets.
Massive pulmonary embolism has been reported to occur with the use of lower extremity tourniquets. We used transesophageal echocardiography to determine the incidence of venous embolism during lower extremity orthopedic surgery performed with a pneumatic tourniquet. The hemodynamic and respiratory consequences of all embolic events were assessed. Venous emboli were detected after tourniquet deflation in 8 of 30 procedures. The incidence of embolism was unrelated to the type of surgical procedure performed or the duration of tourniquet inflation. There were no significant differences in preoperative characteristics or postdeflation hemodynamic and respiratory responses between patients with and without emboli. Venous embolization is a relatively common event after tourniquet deflation. The clinical significance of these events remains to be determined.
Adult↗