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1.
Nature ; 569(7757): E9, 2019 May.
Article in English | MEDLINE | ID: mdl-31073227

ABSTRACT

Change history: In this Letter, the y-axis values in Fig. 3f should go from 4 to -8 (rather than from 4 to -4), the y-axis values in Fig. 3h should appear next to the major tick marks (rather than the minor ticks), and in Fig. 1b, the arrows at the top and bottom of the electron-scale current sheet were going in the wrong direction; these errors have been corrected online.

2.
Med Sante Trop ; 29(1): 61-67, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-31031250

ABSTRACT

The objective of this work was to identify possible correlations between physicochemical parameters (water temperature, water flow velocity, electrical conductivity, dissolved oxygen, salinity, pH, nitrates, and phosphates) and the spatial distribution in the Senegal River delta of snail species that are intermediate hosts of human schistosomes. Eight water points (ME1 to ME4, NE1 and NE2, TA1 and TA2) were selected in the villages of Menguègne Boye, Ndellé Boye, and Thilla for biweekly monitoring of these snails and the physicochemical parameters of the water. The results show that the spatial distribution of the snail populations is related to pH, dissolved oxygen (mg/l), conductivity, temperature (̊C), and water flow velocity (m/s).


Subject(s)
Disease Vectors , Rivers , Snails/physiology , Snails/parasitology , Animals , Hydrogen-Ion Concentration , Oxygen/analysis , Population Density , Schistosoma/isolation & purification , Schistosoma/physiology , Senegal , Temperature , Water/chemistry
3.
Nature ; 557(7704): 202-206, 2018 05.
Article in English | MEDLINE | ID: mdl-29743689

ABSTRACT

Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, this process occurs in a minuscule electron-scale diffusion region1,2. On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed3-5. Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region 6 . In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales7-11. However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.

4.
Geophys Res Lett ; 45(10): 4569-4577, 2018 May 28.
Article in English | MEDLINE | ID: mdl-31031447

ABSTRACT

Magnetospheric Multiscale observations are used to probe the structure and temperature profile of a guide field reconnection exhaust ~100 ion inertial lengths downstream from the X-line in the Earth's magnetosheath. Asymmetric Hall electric and magnetic field signatures were detected, together with a density cavity confined near 1 edge of the exhaust and containing electron flow toward the X-line. Electron holes were also detected both on the cavity edge and at the Hall magnetic field reversal. Predominantly parallel ion and electron heating was observed in the main exhaust, but within the cavity, electron cooling and enhanced parallel ion heating were found. This is explained in terms of the parallel electric field, which inhibits electron mixing within the cavity on newly reconnected field lines but accelerates ions. Consequently, guide field reconnection causes inhomogeneous changes in ion and electron temperature across the exhaust.

5.
Phys Rev Lett ; 117(18): 185102, 2016 Oct 28.
Article in English | MEDLINE | ID: mdl-27835012

ABSTRACT

Observations made using the Wind spacecraft of Hall magnetic fields in solar wind reconnection exhausts are presented. These observations are consistent with the generation of Hall fields by a narrow ion inertial scale current layer near the separatrix, which is confirmed with an appropriately scaled particle-in-cell simulation that shows excellent agreement with observations. The Hall fields are observed thousands of ion inertial lengths downstream from the reconnection X line, indicating that narrow regions of kinetic dynamics can persist extremely far downstream.

6.
Geophys Res Lett ; 43(10): 4716-4724, 2016 05 28.
Article in English | MEDLINE | ID: mdl-27635105

ABSTRACT

New Magnetospheric Multiscale (MMS) observations of small-scale (~7 ion inertial length radius) flux transfer events (FTEs) at the dayside magnetopause are reported. The 10 km MMS tetrahedron size enables their structure and properties to be calculated using a variety of multispacecraft techniques, allowing them to be identified as flux ropes, whose flux content is small (~22 kWb). The current density, calculated using plasma and magnetic field measurements independently, is found to be filamentary. Intercomparison of the plasma moments with electric and magnetic field measurements reveals structured non-frozen-in ion behavior. The data are further compared with a particle-in-cell simulation. It is concluded that these small-scale flux ropes, which are not seen to be growing, represent a distinct class of FTE which is generated on the magnetopause by secondary reconnection.

7.
Int J STD AIDS ; 23(11): 775-80, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23155096

ABSTRACT

Secondary analysis of the PID Evaluation and Clinical Health (PEACH) data suggests that among women presenting with signs and symptoms of pelvic inflammatory disease (PID), those who reported oral sex were less likely to have endometritis (adjusted odds ratio [OR] 0.5 [0.3-0.8]) than those who did not report oral sex. Adaptive immunity requires antigenic priming of the lymphatic system. As lymphatic tissue is abundant in the oropharynx, oral sex could lead to effective immune stimulation and prevent PID. To determine whether oral sex could be a protective factor for PID the relationship between self-reported oral sex and endometritis was analysed among 619 women with clinically suspected PID who participated in the PEACH study. Nearly one quarter of participants reported oral sex in the past four weeks. These women also reported a higher number of sexual partners, a new partner within the past four weeks and a higher frequency of sexual intercourse (all P < 0.03). They were more likely to smoke (P < 0.0001), drink alcohol (P < 0.004) and use recreational drugs (P < 0.02). Participants reporting oral sex were significantly less likely to be black or to have a positive test for Neisseria gonorrhoeae (7.8% versus 21.6%, P = 0.001). Women who disclosed oral sex were significantly less likely to have endometritis after adjusting for race, number of partners, recent new partner, smoking, alcohol use and drug use (adjusted OR 0.5 [0.3-0.8]). This is the first paper showing a negative association between oral sex and endometritis. This may be mediated by a protective immune response in the genital tract following priming in the oropharynx. This hypothesis needs to be tested in further studies.


Subject(s)
Endometritis/epidemiology , Endometritis/prevention & control , Pelvic Inflammatory Disease/complications , Pelvic Inflammatory Disease/epidemiology , Sexual Behavior , Adolescent , Adult , Female , Humans , Prunus , Young Adult
8.
J Physiol ; 589(Pt 4): 939-51, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21173078

ABSTRACT

The renin­angiotensin system (RAS) regulates blood pressure mainly via the actions of angiotensin (Ang)II, generated via angiotensin converting enzyme (ACE). The ACE homologue ACE2 metabolises AngII to Ang1-7, decreasing AngII and increasing Ang1-7, which counteracts AngII activity via the Mas receptor. However, ACE2 also converts AngI to Ang1-9, a poorly characterised peptide which can be further converted to Ang1-7 via ACE. Ang1-9 stimulates bradykinin release in endothelium and has antihypertrophic actions in the heart, attributed to its being a competitive inhibitor of ACE, leading to decreased AngII, rather than increased Ang1-7. To date no direct receptor-mediated effects of Ang1-9 have been described. To further understand the role of Ang1-9 in RAS function we assessed its action in cardiomyocyte hypertrophy in rat neonatal H9c2 and primary adult rabbit left ventricular cardiomyocytes, compared to Ang1-7. Cardiomyocyte hypertrophy was stimulated with AngII or vasopressin, significantly increasing cell size by approximately 1.2-fold (P < 0.05) as well as stimulating expression of the hypertrophy gene markers atrial natriuretic peptide, brain natriuretic peptide, ß-myosin heavy chain and myosin light chain (2- to 5-fold, P < 0.05). Both Ang1-9 and Ang1-7 were able to block hypertrophy induced by either agonist (control, 186.4 µm; AngII, 232.8 µm; AngII+Ang1-7, 198.3 µm; AngII+Ang1-9, 195.9 µm; P < 0.05). The effects of Ang1-9 were not inhibited by captopril, supporting previous evidence that Ang1-9 acts independently of Ang1-7. Next, we investigated receptor signalling via angiotensin type 1 and type 2 receptors (AT1R, AT2R) and Mas. The AT1R antagonist losartan blocked AngII-induced, but not vasopressin-induced, hypertrophy. Losartan did not block the antihypertrophic effects of Ang1-9, or Ang1-7 on vasopressin-stimulated cardiomyocytes. The Mas antagonist A779 efficiently blocked the antihypertrophic effects of Ang1-7, without affecting Ang1-9. Furthermore, Ang1-7 activity was also inhibited in the presence of the bradykinin type 2 receptor antagonist HOE140, without affecting Ang1-9. Moreover, we observed that the AT2R antagonist PD123,319 abolished the antihypertrophic effects of Ang1-9, without affecting Ang1-7, suggesting Ang1-9 signals via the AT2R. Radioligand binding assays demonstrated that Ang1-9 was able to bind the AT2R (pKi = 6.28 ± 0.1). In summary, we ascribe a direct biological role for Ang1-9 acting via the AT2R. This has implications for RAS function and identifying new therapeutic targets in cardiovascular disease.


Subject(s)
Angiotensin II/physiology , Angiotensin I/physiology , Myocytes, Cardiac/pathology , Peptide Fragments/physiology , Receptor, Angiotensin, Type 2/physiology , Signal Transduction/physiology , Angiotensin I/pharmacology , Angiotensin II/pharmacology , Animals , Animals, Newborn , Cell Line, Transformed , Cell Survival/physiology , Cells, Cultured , HeLa Cells , Humans , Hypertrophy/pathology , Myocytes, Cardiac/physiology , Peptide Fragments/pharmacology , Rabbits , Rats
9.
Sex Transm Infect ; 86(1): 29-31, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19703841

ABSTRACT

OBJECTIVE: Mycoplasma genitalium has been identified as a cause of pelvic inflammatory disease (PID), a clinical syndrome associated with inflammation of the female upper genital tract and serious reproductive sequelae. As the demographic, behavioural and sexual risk profile of women with M genitalium-associated PID is not well understood, the characteristics of M genitalium-infected women presenting with clinically suspected PID were investigated. METHODS: Data from 586 participants in the PID Evaluation and Clinical Health Study were analysed. Demographic, sexual history and behavioural characteristics, including age, race, marital status, education level, sexual activity, number of sexual partners, history of sexually transmitted infection (STI), bacterial vaginosis and PID, contraception use, oral and anal sex, age at sexual debut, douching practices and drug, alcohol and tobacco use, were compared between 88 women testing positive and 498 women testing negative for M genitalium by PCR in the cervix and/or endometrium. Twenty-two women with M genitalium mono-infections were compared with 172 women who tested positive for Neisseria gonorrhoeae by culture and/or Chlamydia trachomatis by PCR. RESULTS: Age under 25 years, douching two or more times per month and smoking were independently associated with M genitalium. Women with M genitalium mono-infections were significantly less likely to be African-American (59.1% vs 86.0%, p = 0.001) than women with N gonorrhoeae and/or C trachomatis. CONCLUSIONS: Women infected with M genitalium had some characteristics commonly associated with PID and other STI. The demographic, sexual and behavioural characteristics of M genitalium-positive women were similar to women with chlamydial and/or gonococcal PID.


Subject(s)
Mycoplasma Infections/complications , Mycoplasma genitalium/isolation & purification , Pelvic Inflammatory Disease/microbiology , Sexual Behavior , Adult , Age Factors , Cervix Uteri/microbiology , Cohort Studies , Endometrium/microbiology , Female , Humans , Mycoplasma Infections/transmission , Risk Factors , Smoking/adverse effects , Vaginal Douching/adverse effects , Young Adult
10.
Sex Transm Infect ; 85(4): 242-8, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19004865

ABSTRACT

OBJECTIVES: As the aetiology of bacterial vaginosis (BV) is not well understood, this study sought to determine the relationships between several fastidious microbes, BV and selected clinical characteristics of BV. METHODS: Endometrial and cervical specimens from 50 women with non-gonococcal, non-chlamydial endometritis were tested for Leptotrichia sanguinegens/amnionii, Atopobium vaginae, bacterial vaginosis-associated bacteria 1 (BVAB1), Ureaplasma urealyticum biovar 2 (UU-2) and Ureaplasma parvum using PCR. BV was categorised using Nugent's and Amsel's criteria. Odds ratios (OR) adjusted for age and race were estimated using multivariable logistic regression. RESULTS: Although elevated pH was a universal feature, other BV characteristics differed by pathogen, suggesting variable clinical presentation. Only UU-2 was strongly associated with vaginal discharge, but a positive whiff test and a 20% or greater classification of epithelial cells as clue cells were more common among women with L sanguinegens/amnionii, A vaginae and BVAB1. For each of these bacteria, there were trends towards associations with BV defined by Amsel's criteria (L sanguinegens/amnionii OR 2.9, 95% CI 0.5 to 15.7; A vaginae OR 2.6, 95% CI 0.6 to 11.4; BVAB1 OR 5.7, 95% CI 1.0 to 31.1) and significant associations with BV defined by Gram stain (L sanguinegens/amnionii OR 17.7, 95% CI 2.8 to 113.0; A vaginae OR 19.2, 95% CI 3.7 to 98.7; BVAB1 OR 21.1, 95% CI 2.2 to 198.5). CONCLUSIONS: L sanguinegens/amnionii, A vaginae and BVAB1 are associated with clinical characteristics consistent with BV and BV defined by Nugent's and Amsel's criteria. These fastidious bacteria may cause unrecognised infection, as none was associated with abnormal vaginal discharge.


Subject(s)
Actinobacteria/isolation & purification , Leptotrichia/isolation & purification , Ureaplasma/isolation & purification , Vaginal Discharge/microbiology , Vaginosis, Bacterial/microbiology , Adolescent , Adult , Biopsy , False Negative Reactions , Female , Humans , Hydrogen-Ion Concentration , Logistic Models , Male , Odorants , Pelvic Inflammatory Disease/microbiology , Polymerase Chain Reaction/methods , Random Allocation , Risk Factors , Ureaplasma/classification , Uterus/microbiology , Uterus/pathology , Vaginosis, Bacterial/diagnosis , Young Adult
11.
Sex Transm Infect ; 84(5): 338-42, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18445635

ABSTRACT

OBJECTIVES: As Mycoplasma genitalium is associated with pelvic inflammatory disease (PID), we examined the efficacy of a commonly used PID antimicrobial in treating M genitalium upper genital tract infection. METHODS: In the PID Evaluation and Clinical Health study of inpatient versus outpatient treatment, 682 women treated with cefoxitin and doxycycline for clinically suspected PID had stored cervical and endometrial specimens available for analysis. In the current sub study, we compared baseline endometritis, short term treatment failure (continued endometritis and pelvic pain 30 days following treatment) and sequelae among women with and without M genitalium, identified using PCR. RESULTS: Endometrial M genitalium was associated with baseline endometritis (adjusted OR 3.0, 95% CI 1.5 to 6.1). Among women with a positive baseline M genitalium test, 41% tested positive again 30 days following treatment. Women testing positive compared to those testing negative for M genitalium at baseline had an increased risk of short-term treatment failure (RR 4.6, 95% CI 1.1 to 20.1). Rates of sequelae, including infertility (22%), recurrent PID (31%) and chronic pelvic pain (42%), were high among women testing positive for endometrial M genitalium at baseline. There was a non-significant trend towards increased infertility, chronic pelvic pain and recurrent PID, and decreased pregnancy and live birth following M genitalium infection. CONCLUSIONS: M genitalium is associated with endometritis and short-term PID treatment failure. Cefoxitin and doxycycline, a Centers for Disease Control and Prevention recommended PID treatment regimen, is ineffective for the treatment of M genitalium upper genital tract infection.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Cefoxitin/therapeutic use , Doxycycline/therapeutic use , Endometritis/drug therapy , Mycoplasma Infections/drug therapy , Mycoplasma genitalium , Adult , Aged , Drug Therapy, Combination , Endometritis/microbiology , Female , Humans , Infertility, Female/microbiology , Middle Aged , Pelvic Inflammatory Disease/drug therapy , Pelvic Inflammatory Disease/microbiology , Recurrence , Risk Factors , Treatment Failure
12.
Mech Ageing Dev ; 129(3): 129-37, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18160096

ABSTRACT

The 'membrane pacemaker' hypothesis provides a putative mechanistic linkage between variations in energy metabolism, rates of ageing and lifespan across different species. Within species we have found positive associations between longevity and metabolism, which contrast the inter-specific trends. It is of interest to know therefore how levels of lipid desaturation in membranes are linked to variation in metabolism between individuals within species. We explored this problem by extracting membrane fatty acids from the livers of mice that varied in their metabolic rate, in a strain (MF1) where we have previously demonstrated a positive association between metabolism and lifespan. We measured resting metabolic rate (RMR) in 60 mice, each measured on three occasions, and measured their body compositions using dual energy X-ray absorptiometry (DXA). We selected 28 individuals that exhibited a wide variation in their mean resting metabolic rates (RMR) and extracted membrane lipids from the livers of these mice post mortem and analysed them for the patterns of contribution of different fatty acids. We then sought associations between the levels of membrane desaturation and the individual variability in RMR, using the proportional contributions of each fatty acid as predictors in a stepwise regression or by re-describing the variation in fatty acyl lipids using a PCA analysis and then seeking associations between scores on the derived components and RMR. We used whole animal RMRs and also RMR with the effects of body composition (fat free mass) removed. The level of individual variation in RMR was consistent with our previous observations. There was a significant positive association (p=0.019) between the proportion of palmitic acid (16:0) in the membranes and RMR, which was strengthened (p=0.014) when we adjusted RMR for differences in fat free mass. The proportion of palmitic acid (16:0) explained 20.9% of the individual variation in residual RMR. There was no association between RMR or mass adjusted RMR and the proportional representation of any other fatty acid, including 22:6 (DHA) predicted by the membrane pacemaker hypothesis to be of particular significance. High levels of saturated fatty acids in the membranes of mice with high rates of metabolism may contribute to their greater longevity, but the mechanism tying together increased membrane saturation with elevated RMR remains unclear.


Subject(s)
Basal Metabolism , Fatty Acids/analysis , Liver/metabolism , Longevity , Membrane Lipids/chemistry , Animals , Male , Mice , Palmitic Acid/analysis
13.
Pharmacogenomics J ; 5(5): 305-23, 2005.
Article in English | MEDLINE | ID: mdl-16044165

ABSTRACT

The blueprint for cellular diversity and response to environmental change is encoded in the cis-acting regulatory sequences of most genes. Deciphering this 'cis-regulatory code' requires multivariate data sets that examine how these regions coordinate transcription in response to diverse environmental stimuli and therapeutic treatments. We describe a transcriptional approach that profiles the activation of multiple transcriptional targets against combinatorial arrays of therapeutic and signal transducing agents. Application of this approach demonstrates how cis-element composition and promoter context combine to influence transcription downstream of mitogen-induced signaling networks. Computational dissection of these transcriptional profiles in activated T cells uncovers a novel regulatory synergy between IGF-1 and CD28 costimulation that modulates NF-kappaB and AP1 pathways through signaling cascades sensitive to cyclosporin A and wortmannin. This approach provides a broader view of the hierarchical signal integration governing gene expression and will facilitate a practical design of combinatorial therapeutic strategies for exploiting critical control points in transcriptional regulation.


Subject(s)
CD28 Antigens/biosynthesis , Gene Expression Regulation/genetics , Promoter Regions, Genetic/drug effects , T-Lymphocytes/metabolism , Transcription, Genetic/drug effects , Algorithms , CD28 Antigens/genetics , Cells, Cultured , Gene Expression Profiling/methods , Gene Targeting/methods , Genes, Reporter , Humans , Immunologic Factors/pharmacology , Insulin-Like Growth Factor I/biosynthesis , Insulin-Like Growth Factor I/genetics , Interleukin-2/biosynthesis , Interleukin-2/genetics , Jurkat Cells , Lymphocyte Activation/drug effects , Mitogens/pharmacology , Models, Genetic , Oligonucleotide Array Sequence Analysis , Principal Component Analysis , Signal Transduction/genetics , T-Lymphocytes/drug effects , Time Factors , Transfection
14.
Am J Respir Cell Mol Biol ; 24(5): 616-20, 2001 May.
Article in English | MEDLINE | ID: mdl-11350832

ABSTRACT

Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of several diseases including airway inflammation of asthma. iNOS is active only as a homodimer. We previously demonstrated that the region encoded by exons 8 and 9 is critical for dimerization. In this study, alanine-scanning mutagenesis was used to identify critical amino acids in that region by expression of mutant proteins in human embryonic kidney 293 cells. All iNOS mutants yielded iNOS protein as detected by Western analysis. Four iNOS mutants with alanine replacing Trp260, Asn261, Tyr267, or Asp280 did not generate NO. Dimer formation was tested by sodium dodecyl sulfate polyacrylamide gel electrophoresis at 4 degrees C, followed by immunoblotting. Wild-type iNOS migrated both as monomers and dimers. iNOS mutants with alanine replacing Trp260, Asn261, or Tyr267, however, migrated only as monomers, suggesting that their inability to produce NO is related to a defect in dimer formation. Interestingly, the Asp280 mutant retained the ability to dimerize, indicating that it represents an inactive form of an iNOS dimer. These data identify four amino acids in exons 8 and 9 critical for iNOS activity, three of which also influence dimerization. These residues are strictly conserved among all NOS isforms and across species. Thus all NOS isoforms share general structural similarities, including specific amino acids critical for dimerization and catalytic activity. These data increase our understanding of the structural elements critical for NO synthesis and lay the groundwork for future studies aimed at downregulation of iNOS activity.


Subject(s)
Exons/genetics , Nitric Oxide Synthase/chemistry , Nitric Oxide Synthase/genetics , Alanine/genetics , Amino Acid Substitution/genetics , Binding Sites/physiology , Blotting, Western , Cell Line , Conserved Sequence , Dimerization , Electrophoresis, Polyacrylamide Gel , Enzyme Activation/physiology , Humans , Kidney/cytology , Kidney/metabolism , Molecular Sequence Data , Mutagenesis, Site-Directed , Nitric Oxide Synthase Type II , Protein Structure, Tertiary/physiology , Sequence Homology, Amino Acid , Structure-Activity Relationship , Transfection
15.
J Biol Chem ; 276(29): 27647-56, 2001 Jul 20.
Article in English | MEDLINE | ID: mdl-11313336

ABSTRACT

In this report, we explore the mechanisms of targeting of p300 to the interleukin-2 (IL-2) promoter in response to mitogenic and oncogenic molecular signals. Recruitment of p300 by cAMP-responsive element-binding protein-Rel cross-talk at the composite CD28 response element (CD28RE)-TRE element of the IL-2 promoter is essential for promoter inducibility during T-cell activation, and CD28RE-TRE is the exclusive target of the human T-cell lymphotropic virus type I oncoprotein Tax. The intrinsic histone acetyltransferase activity of p300 is dispensable for activation of the IL-2 promoter, and the N-terminal 743 residues contain the minimal structural requirements for synergistic transactivation of the CD28RE-TRE, the IL-2 promoter, and endogenous IL-2 gene expression. Mutational analysis of p300 reveals differential structural requirements for the N-terminal p300 module by individual cis-elements within the IL-2 promoter. These findings provide evidence that p300 assembles at the IL-2 promoter to form an enhanceosome-like signal transduction target that is centrally integrated at the CD28RE-TRE element of the IL-2 promoter through specific protein module-targeted associations in activated T-cells.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Interleukin-2/genetics , Mitogens/metabolism , Nuclear Proteins/metabolism , Promoter Regions, Genetic , Receptor Cross-Talk , Signal Transduction , T-Lymphocytes/metabolism , Trans-Activators/metabolism , Base Sequence , CD28 Antigens/genetics , DNA Primers , Humans , Jurkat Cells , Lymphocyte Activation , T-Lymphocytes/immunology , Transcriptional Activation
16.
J Neurosurg ; 93(2 Suppl): 259-65, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11012057

ABSTRACT

OBJECT: Interbody fusion devices are rapidly gaining acceptance as a method of ensuring lumbar interbody arthrodesis. Although different types of devices have been developed, the comparative reconstruction stability remains controversial. It also remains unclear how different stress-shielded environments are created within the devices. Using a calf spine model, this study was designed to compare the construct stiffness afforded by 11 differently designed lumbar interbody fusion devices and to quantify their stress-shielding effects by measuring pressure within the devices. METHODS: Sixty-six lumbar specimens obtained from calves were subjected to anterior interbody reconstruction at L4-5 by using one of the following interbody fusion devices: four different threaded fusion cages (BAK device, BAK Proximity, Ray TFC, and Danek TIBFD), five different nonthreaded fusion devices (oval and circular Harms cages, Brantigan PLIF and ALIF cages, and InFix device); two different types of allograft (femoral ring and bone dowel) were used. Construct stiffness was evaluated in axial compression, torsion, flexion, and lateral bending. Prior to testing, a silicon elastomer was injected into the cages and intracage pressures were measured using pressure needle transducers. CONCLUSIONS: No statistical differences were observed in construct stiffness among the threaded cages and nonthreaded devices in most of the testing modalities. Threaded fusion cages demonstrated significantly lower intracage pressures compared with nonthreaded cages and structural allografts. Compared with nonthreaded cages and structural allografts, threaded fusion cages afforded equivalent reconstruction stiffness but provided more stress-shielded environment within the devices.


Subject(s)
Lumbar Vertebrae/surgery , Orthopedic Fixation Devices , Spinal Fusion/instrumentation , Animals , Biomechanical Phenomena , Cattle , Equipment Design , Materials Testing , Pressure , Stress, Mechanical
17.
Br J Ophthalmol ; 84(9): 1031-4, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10966960

ABSTRACT

BACKGROUND: The safety and predictability of refractive surgery for all degrees of myopia is now becoming established. It is therefore appropriate to evaluate whether there is a patient driven demand for such treatments and, if so, to establish guidelines for its provision within the National Health Service (NHS). METHODS: A comparative study was designed to assess the effect of degree of myopia on quality of life ("high" (n = 30) -10.00D, worse eye; "moderate" (n = 40) -4.00 to -9.75D, worse eye; "low" (n = 42) <-4. 00D, worse eye) compared with a group of patients with keratoconus (n = 30) treated by optical correction. Data collection included binocular logMAR visual acuity, Pelli-Robson low contrast letter sensitivity, questionnaires to assess subjective visual function (VF-14) and effect on quality of life (VQOL), and semi-structured interviews. RESULTS: There were no significant differences in any of the measures between patients with a high degree of myopia and those with keratoconus, or between those with a low and those with a moderate degree of myopia. However, those with a high degree of myopia had highly significantly poorer logMAR, VF-14, and VQOL scores than those with low and moderate myopia (p<0.001). Interview data supported these findings with patients with a high degree of myopia and those with keratoconus reporting that psychological, cosmetic, practical, and financial factors affected their quality of life. CONCLUSION: Compared with low and moderate myopia, patients with a high degree of myopia experience impaired quality of life similar to that of patients with keratoconus. Criteria should therefore be identified to enable those in sufficient need to obtain refractive surgical treatment under the NHS.


Subject(s)
Myopia/surgery , Quality of Life , Adolescent , Adult , Aged , Female , Health Services Needs and Demand , Humans , Keratotomy, Radial , Male , Middle Aged , Practice Guidelines as Topic/standards , State Medicine , Surveys and Questionnaires
18.
J Spinal Disord ; 13(1): 58-62, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10710152

ABSTRACT

This study examines the biomechanical effects of interbody cages and variations in posterior rod diameter in a simulated single-level spinal fusion. A single-level spinal fusion model composed of polyethylene cylinders, posterior pedicular instrumentation, and variously positioned single or dual interbody cages was used for biomechanical testing. Constructs were tested under compressive flexural load, with measurement of stiffness, rod strain, cage strain, and intracage pressure. A strong linear correlation emerged between the mean construct stiffness and cage positioning within the sagittal plane that was inversely related to posterior rod strain. Two small titanium mesh cages were equivalent to one large cage. In a single-level spine model, the presence of and sagittal position of interbody cages significantly influences overall construct stiffness. Cage strain increased with more anterior positions and was inversely related to rod strain.


Subject(s)
Internal Fixators , Materials Testing , Spinal Fusion/instrumentation , Humans , Pressure , Stainless Steel , Titanium , Weight-Bearing
19.
Spine (Phila Pa 1976) ; 24(22): 2300-6; discussion 2307, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10586452

ABSTRACT

STUDY DESIGN: This static, nondestructive, in vitro biomechanical study examines anterior solid rod construct stiffness following the addition of multilevel, threaded cortical bone dowels in a bovine model. A comparison is made with a clinically relevant posterior construct with and without an anterior release. OBJECTIVES: To determine if the addition of solid, multilevel disc space implants will increase construct rigidity, while maintaining or enhancing anterior column length. SUMMARY OF BACKGROUND DATA: Anterior instrumentation for thoracolumbar and lumbar scoliosis has achieved greater correction and preserved distal motion segments; however, kyphosis over the instrumented segments and nonunion have been observed more frequently than with posterior segmental spinal instrumentation. METHOD: Fifteen calf spines underwent mechanical testing. Group A (n = 7) included anterior constructs: 1) intact, 2) anterior release/rod/rib graft (L2-L5), and 3) anterior release/rod/dowels (L2-L5). Group B (n = 8) included posterior constructs: 1) intact, 2) posterior rod without anterior release (T13-L5), 3) posterior rod (T13-L5)/anterior release/rib graft (L2-L5). The protocol included axial compression (-600 N), axial rotation (+7 Nm), flexion/extension (+7.5 Nm), and lateral bending (+7.5 Nm). An anterior extensometer measured segmental displacements to calculate construct stiffness. Lateral radiographs evaluated alignment for the anterior constructs. Statistical analysis involved a one way analysis of variance (ANOVA) and a Student-Newman-Keuls post hoc test. RESULTS: All reconstructions restored stiffness to intact values with the exception of the dowels alone in axial rotation. The rod/dowel construct was stiffer than all other groups in axial compression, flexion/extension, and lateral bending, with the exception of the posterior rod without discectomy, which was superior in flexion and statistically similar in extension, lateral bending, and axial rotation. The anterior construct with rib graft was equivalent to the posterior construct with rib graft in all modes of testing. The dowels created greater lordosis than the bicortical rib grafts. CONCLUSIONS: Disc space augmentation increased stiffness except in axial rotation, in which values were restored to the intact level. Stiffness was superior to a clinically relevant posterior instrumentation comparison group following anterior release, and was equivalent to a posterior construct without anterior release except in anterior flexion. In addition, the implants enhanced lordosis. Increased rigidity should improve rates of arthrodesis, while maintenance of sagittal alignment may prevent pathologic compensatory curves in adjacent spinal segments. Further research is required to determine the optimal method of achieving structural interspace support.


Subject(s)
Bone Nails , Bone Transplantation , Animals , Cattle , Materials Testing , Ribs/transplantation , Scoliosis/surgery , Stress, Mechanical
20.
Spine (Phila Pa 1976) ; 24(22): 2377-82, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10586464

ABSTRACT

STUDY DESIGN: The stabilizing effects of five different occipitocervical fixations were compared. OBJECTIVES: To evaluate the construct stability provided by five different occipito-atlanto-axial fixation techniques. SUMMARY OF BACKGROUND DATA: Few studies have addressed occipitocervical reconstruction stability and no studies to data have investigated anterior-posterior translational stiffness. METHODS: A total of 21 human cadaveric spines were used. After testing intact spines (CO-C2), a type II dens fracture was created and five different reconstructions were performed: 1) occipital and sublaminar wiring/rectangular rod, 2) occipital screws and C2 lamina claw hooks/rod, 3) occipital screws, foramen magnum screws, and C1-C2 transarticular screws/rod, 4) occipital screws and C1-C2 transarticular screws/Y-plate, and 5) occipital screws and C2 pedicle screws/rod. Biomechanical testing parameters included axial rotation, flexion/extension, lateral bending, and anterior-posterior translation. RESULTS: Pedicle screw fixation demonstrated the highest stiffness among the five reconstructions (P < 0.05). The two types of transarticular screw methods provided greater stability than hook or wiring reconstructions (P < 0.05). The C2 claw hook technique resulted in greater stability than sublaminar wiring fixation in anterior-posterior translation (P < 0.05). However, the wiring procedure did not significantly increase the stiffness levels beyond the intact condition under anterior-posterior translation and lateral bending (P > 0.05). DISCUSSION: C2 transpedicular and C1-C2 transarticular screws significantly increased the stabilizing effect compared to sublaminar wiring and lamina hooks. The improved stability afforded by C2 pedicular and C1-C2 transarticular screws offer many potential advantages including a high rate of bony union, early ambulation, and easy nursing care. CONCLUSION: Occipitocervical reconstruction techniques using C1-C2 transarticular screws or C2 pedicle screws offer biomechanical advantages compared to sublaminar wiring or lamina hooks. Pedicle screw fixation exhibited the highest construct stiffness among the five reconstructions.


Subject(s)
Atlanto-Axial Joint/surgery , Atlanto-Occipital Joint/surgery , Spinal Fusion/methods , Aged , Atlanto-Axial Joint/physiology , Atlanto-Occipital Joint/physiology , Biomechanical Phenomena , Bone Nails , Bone Screws , Bone Wires , Cadaver , Female , Humans , Male , Spinal Fusion/instrumentation
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