Adverse reactions to vaccines in the tropics.
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Female↗
Biomedical subjects
A Hall
Publications and source records attributed to A Hall.
The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania.
We evaluated the effect of weekly doses of 400 mg of ferrous sulphate for 4 months on the iron status of adolescent girls in a controlled trial in Tanga, Tanzania. Supplementation led to a significantly greater increase in serum ferritin compared with the control group (+ 15.6 microg/l vs. 8.6 microg/l) (P = 0.002) but there was no significant difference in change in haemoglobin. Children given iron showed a significantly greater weight gain than controls (+ 2.4 kg vs. + 1.4 kg) (P = 0.03). Weekly iron supplementation may be an effective means of increasing iron stores and growth in children vulnerable to iron deficiency.
Adolescent↗
How many people with heart failure are appropriate for biventricular resynchronization?
AIMS: Increasing evidence exists suggesting that biventricular pacing improves outcome and symptoms in severe heart failure if various selection criteria are fulfilled. It is unsure how many people might benefit from this therapy. Our aim was to provide such data. METHODS AND RESULTS: Over one calendar year all patients admitted to a large U.K. District General Hospital, that were classified with a diagnosis of heart failure, were audited. The selection criteria were; (1) severe heart failure (NYHA class III or IV), (2) heart failure due to a dilated cardiomyopathy, (3) QRS duration greater than 120 ms or (4) the presence of a bundle branch block pattern. Subjects were divided into those in sinus rhythm to determine those who would be suitable for atrially synchronized biventricular pacing and those with an abnormally long PR interval (>210 ms) who might additionally benefit from improved atrioventricular synchrony. 1042 patients were coded with heart failure. 721 fulfilled diagnostic criteria and were studied. 202 (28%) had severe heart failure, 178 (25%) had a QRS of at least 120 ms, 437 (61%) had an ischaemic cardiomyopathy, 176 (24%) an idiopathic cardiomyopathy and 433 (60%) were in sinus rhythm. Overall mortality at the time of census was 29%. 43 patients were suitable for biventricular pacing with a further 29 atrial patients fibrillation who might benefit from biventricular pacing alone. CONCLUSION: Using our criteria, approximately 10% of an unselected group of heart failure admitted to a typical U.K. district general hospital over a calendar year would be appropriate for biventricular pacing. This represents a large number of patients who might derive benefit from this new therapy.
Aged↗
Evidence that the cAMP pathway controls emergence of both primary and appressorial germ tubes of barley powdery mildew.
Development of conidia of barley powdery mildew involves the formation of a primary germ tube (PGT), an appressorial germ tube (AGT), and an appressorium. Previously, it was found that cyclic AMP (cAMP) was involved in these developmental processes. Comparison of development on the host surface with two types of cellulose membrane revealed that frequency of PGT emergence was surface independent. On one type of cellulose, where the frequencies of both AGT and appressorial differentiation were similar to that on the host surface, cAMP levels and protein kinase A (PKA) activities had a biphasic pattern with peaks at 15 min and 4 h after inoculation (prior to PGT and AGT emergence, respectively). The effect of manipulating cAMP levels was tested on another type of cellulose membrane, which stimulated a lower degree of AGT and appressorial formation than the host surface. Cholera toxin and forskolin, activators of adenylyl cyclase, significantly increased PGT emergence, but cAMP did not. Cholera toxin, forskolin, and cAMP increased the frequency of AGT and appressorial formation, but in a time-dependent manner.
Cellulose↗
Sex differences in risk factors, treatment and mortality after acute myocardial infarction: an observational study.
BACKGROUND: Coronary heart disease is the major cause of death of postmenopausal women in industrialised countries. Although acute myocardial infarction (AMI) affects men in greater numbers, the short-term outcomes for women are worse. In the longer term, studies suggest that mortality risk for women is lower or similar to that of men. However, length of follow up and adjustment for confounding factors have varied and more importantly, the association between treatment and outcomes has not been examined. STUDY OBJECTIVE: To investigate the association between sex differences in risk factors and hospital treatment and mortality after AMI. DESIGN: A prospective observational study collecting demographic and clinical data on cases of AMI admitted to hospitals in Yorkshire. The main outcome measures were mortality status at discharge from hospital and two years later. SETTING: All district and university hospitals accepting emergency admissions in the former Yorkshire National Health Service (NHS) region of northern England. PARTICIPANTS: 3684 consecutive patients with a possible diagnosis of AMI admitted to hospitals in Yorkshire between 1 September and 30 November 1995. MAIN RESULTS: AMI was confirmed by the attending consultant for 2196 admissions (2153 people, 850 women and 1303 men). Women were older and less likely than men to be smokers or have a history of ischaemic heart disease. Crude inhospital mortality was higher for women (30% versus 19% for men, crude odds ratio of death before discharge for women 1.78, 95% confidence intervals 1.46, 2.18, p=0.00). This difference persisted after adjustment for age, risk factors and comorbidities (adjusted OR 1.29, 95% CI 1.04, 1.63, p=0.02), but was not significant when treatment was taken into account. Women were less likely to be given thrombolysis (37% versus 46%, p<0.01) and aspirin (83% versus 90%, p<0.01), discharged with beta blockers (33% versus 47%, p<0.01) and aspirin (82% versus 88% p<0.01) or be scheduled for angiography, exercise testing or revascularisation. Adjustment for age removed much of the disparity in treatment. Crude mortality rate at two years was higher for women (OR 1.81, 95%CI 1.41, 2.31, p=0.00). Age, existing risk factors and acute treatment accounted for most of this difference, with treatment on discharge having little additional influence. CONCLUSIONS: Patients admitted to hospital with AMI should be offered optimal treatment irrespective of age or sex. Women have a worse prognosis after AMI and under-treatment of older people with aspirin and thrombolysis may be contributing to this.
Adult↗
Sub-optimal ACE-inhibitor prescribing and increased all-cause mortality risk. A critical evaluation of routine clinical care.
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Angiotensin-Converting Enzyme Inhibitors↗
Preoperative cardiopulmonary risk assessment by cardiopulmonary exercise testing.
OBJECTIVE: To review the strategies for identification and subsequent management of high-risk patients that have been proposed to reduce perioperative morbidity and mortality. DATA SOURCES: Articles and published reviews of studies on evaluation and management of patients to reduce perioperative morbidity and mortality. SUMMARY OF REVIEW: Many strategies have been devised to evaluate the perioperative risk in elderly patients, particularly those who are about to undergo major intra-abdominal surgery. An assessment of cardiac and pulmonary responses to exercise-induced stress (i.e. cardiopulmonary exercise testing) using a bicycle ergometer, metabolic cart (to measure oxygen uptake and carbon dioxide excretion) and a 12 lead electrocardiograph has been found to be a non.invasive test that is quick, cheap, easy to perform and requires no special preparation. It has advantages over any other preoperative test by defining operative risk and allowing logical triage according to objective risk assessment. It is able to objectively evaluate the extent of any cardiac failure (by assessing the anaerobic threshold), myocardial ischaemia, provides insight into stroke index, the presence of pulmonary artery hypertension and defines obstructive and restrictive lung disease and ventilation perfusion inequality better than conventional preoperative respiratory function tests. CONCLUSIONS: In patients who are about to undergo major intra-abdominal surgery, preoperative cardiopulmonary exercise testing is an excellent predictor of risk in the postoperative period. No other test is able to offer such a comprehensive preoperative risk evaluation for an operative patient.
Journal Article↗
The circadian clock controls the expression pattern of the circadian input photoreceptor, phytochrome B.
Developmental and physiological responses are regulated by light throughout the entire life cycle of higher plants. To sense changes in the light environment, plants have developed various photoreceptors, including the red/far-red light-absorbing phytochromes and blue light-absorbing cryptochromes. A wide variety of physiological responses, including most light responses, also are modulated by circadian rhythms that are generated by an endogenous oscillator, the circadian clock. To provide information on local time, circadian clocks are synchronized and entrained by environmental time cues, of which light is among the most important. Light-driven entrainment of the Arabidopsis circadian clock has been shown to be mediated by phytochrome A (phyA), phytochrome B (phyB), and cryptochromes 1 and 2, thus affirming the roles of these photoreceptors as input regulators to the plant circadian clock. Here we show that the expression of PHYB::LUC reporter genes containing the promoter and 5' untranslated region of the tobacco NtPHYB1 or Arabidopsis AtPHYB genes fused to the luciferase (LUC) gene exhibit robust circadian oscillations in transgenic plants. We demonstrate that the abundance of PHYB RNA retains this circadian regulation and use a PHYB::Luc fusion protein to show that the rate of PHYB synthesis is also rhythmic. The abundance of bulk PHYB protein, however, exhibits only weak circadian rhythmicity, if any. These data suggest that photoreceptor gene expression patterns may be significant in the daily regulation of plant physiology and indicate an unexpectedly intimate relationship between the components of the input pathway and the putative circadian clock mechanism in higher plants.
Circadian Rhythm↗
Signaling to Rho GTPases.
Rho GTPases regulate many important processes in all eukaryotic cells, including the organization of the actin cytoskeleton, gene transcription, cell cycle progression, and membrane trafficking. Their activity is regulated by signals originating from different classes of surface receptors including G-protein-coupled receptors, tyrosine kinase receptors, cytokine receptors, and adhesion receptors. Recent work has identified multiple mechanisms by which receptors can signal to Rho GTPases and this will be the major focus of this review. In addition, there is growing evidence for cross-talk within the Rho GTPase family as well as between the Rho and Ras GTPase families. These signaling networks are thought to provide the cooperative and coordinated interactions that are crucial for regulating complex biological processes such as cell migration.
Enzyme Activation↗
Pituitary adenylate cyclase activating peptide phase shifts circadian rhythms in a manner similar to light.
The endogenous circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Various cues can reset circadian rhythm phase, thereby entraining the internal rhythm to the environmental cycle, and these effects can be investigated using an in vitro method to measure phase shifts of the SCN. Although pituitary adenylate cyclase activating peptide (PACAP) is localized in retinal inputs to the SCN, it has been reported to alter clock phase only during the subjective day (Hannibal et al., 1997), whereas light alters phase only in the subjective night. In this study we show that PACAP can reset the clock in the photic pattern during the subjective night when applied in 10 pM to 1 nM doses. This appears to be mediated via a glutamatergic mechanism, possibly by potentiation of NMDA currents as is seen at 10-100 pM. Given at higher doses (>10 nM), PACAP shifts in the subjective day, apparently via activation of adenylate cyclase and increased intracellular cAMP. These results indicate dose and phase specificity of the effects of PACAP, and a new role as a transmitter in the retinohypothalamic tract.
Animals↗
Interplay between Rac and Rho in the control of substrate contact dynamics.
BACKGROUND: Substrate anchorage and cell locomotion entail the initiation and development of different classes of contact sites, which are associated with the different compartments of the actin cytoskeleton. The Rho-family GTPases are implicated in the signalling pathways that dictate contact initiation, maturation and turnover, but their individual roles in these processes remain to be defined. RESULTS: We monitored the dynamics of peripheral, Rac-induced focal complexes in living cells in response to perturbations of Rac and Rho activity and myosin contractility. We show that focal complexes formed in response to Rac differentiated into focal contacts upon upregulation of Rho. Focal complexes were dissociated by inhibitors of myosin-II-dependent contractility but not by an inhibitor of Rho-kinase. The downregulation of Rac promoted the enlargement of focal contacts, whereas a block in the Rho pathway not only caused a dissolution of focal contacts but also stimulated membrane ruffling and formation of new focal complexes, which were associated with the advance of the cell front. CONCLUSIONS: Rac functions to signal the creation of new substrate contacts at the cell front, which are associated with the induction of ruffling lamellipodia, whereas Rho serves in the maturation of existing contacts, with both contact types requiring contractility for their formation. The transition from a focal complex to a focal contact is associated with a switch to Rho-kinase dependence. Rac and Rho also influence the development of focal contacts and focal complexes, respectively, through mutually antagonistic pathways.
3T3 Cells↗
IpaC induces actin polymerization and filopodia formation during Shigella entry into epithelial cells.
Shigella proteins that are targeted to host cells by a type III secretion apparatus are essential for reorganization of the cytoskeleton during cell invasion. We have developed a semi-permeabilized cell assay that tests the effects of bacterial proteins on the actin cytoskeleton. The Shigella IpaC protein was found to induce the formation of filopodial and lamellipodial extensions in these semi-permeabilized cells. Microinjection of IpaC into cells, or cellular expression of IpaC also led to the formation of filopodial structures. Monoclonal antibodies (mAbs) directed against the C-terminus of IpaC inhibited the IpaC-induced extensions, whereas an anti-N-terminal IpaC mAb stimulated extensive lamellae formation. Shigella induced foci of actin polymerization in the permeabilized cells and these were inhibited by anti-C-terminal IpaC mAbs. Consistent with a role for IpaC in Shigella-induced cytoskeletal rearrangements during entry, stable transfectants expressing IpaC challenged with Shigella showed increased bacterial internalization. IpaC-induced extensions were inhibited by a dominant-interfering form of Cdc42 or the Cdc42-binding domain of WASP, whereas a dominant-interfering form of Rac resulted in inhibition of lamellae formation. We conclude that IpaC leads to activation of Cdc42 which in turn, causes activation of Rac, both GTPases being required for Shigella entry.
3T3 Cells↗
Multiple sclerosis and hepatitis B vaccine?
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Demyelinating Diseases↗
Cloning, central nervous system expression and chromosomal mapping of the mouse PAK-1 and PAK-3 genes.
Two cDNAs encoding PAK kinases were isolated from a mouse embryo library by screening with a PCR-generated probe derived from the kinase domain of a rat PAK kinase. These cDNAs, designated PAK-1 and PAK-3, encode mouse PAK kinases of 545 and 544 amino acids, respectively. Both proteins possess an N-terminal Cdc42/Rac interacting binding domain (CRIB) and a C-terminal serine/threonine kinase domain. Comparison of the two mouse PAK kinases revealed that the proteins show 87% amino acid identity. Northern analysis of a multiple mouse tissue blot with a PAK-1 probe detected a 3.0kb transcript that was almost exclusively expressed in the brain and spinal cord compared to other tissues such as lung, liver and kidney. A similar pattern of central nervous system tissue expression of PAK-3 transcripts of 3.6 and 8kb was also observed. Analysis of two multilocus genetic crosses localized Pak1 and Pak3 to a position on chromosome 7 and X, respectively. The high level of PAK-1 and PAK-3 kinase expression in the mouse brain and spinal cord suggests a potentially important role for these kinases in the control of the cellular architecture and/or signaling in the central nervous system.
Amino Acid Sequence↗
Rho GTPases control polarity, protrusion, and adhesion during cell movement.
Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair and to direct cells to sites of infection. Animal cells move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly of actin filaments. The small GTPases, Rho, Rac, and Cdc42, regulate the organization of actin filaments and we have analyzed their contributions to the movement of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the localization of lamellipodial activity to the leading edge and the reorientation of the Golgi apparatus in the direction of movement. Rho is required to maintain cell adhesion during movement, but stress fibers and focal adhesions are not required. Finally, Ras regulates focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.
Animals↗
Simultaneous measurement of tyrosine hydroxylase activity and phosphorylation in bovine adrenal chromaffin cells.
A method for simultaneous measurement of tyrosine hydroxylase (TH) activation and phosphorylation in permeabilised and intact bovine adrenal chromaffin cells (BACCs) was established. Permeabilised cells were stimulated with cyclic AMP (1--10 microM) in the presence of [32P]ATP and L-[carboxyl-(14)C]tyrosine. Intact BACCs were preincubated with 32P(i) for 3 h and stimulated with forskolin (1--5 microM) in the presence of L-[carboxyl-(14)C]tyrosine. On stimulation each well was covered with a sealed 'chimney' fitted with a small plastic cup containing 300 microl of 1.0 M NaOH that trapped the 14CO(2) released. TH activity was determined by measuring 14C radioactivity. TH phosphorylation was measured in the same cells by separating the solubilized proteins on SDS PAGE followed by autoradiography and/or HPLC analysis. It was found that H89, a protein kinase A inhibitor, significantly blocked both TH phosphorylation and activation in response to cyclic AMP in permeabilised cells. However, in intact cells, H89 was effective only in respect to forskolin-stimulated TH activity and did not block the forskolin-stimulated TH phosphorylation of Ser-40. The reason(s) for this lack of correlation between TH activation and phosphorylation is presently not understood.
Adrenal Medulla↗
A role for Rho-like GTPases in the polarisation of mouse eight-cell blastomeres.
Polarisation of cells during mouse preimplantation development first occurs within blastomeres at the eight-cell stage, as part of a process called compaction. Cell-cell contact mediated by the cell adhesion molecule uvomorulin (E-cadherin) and the activity of the microfilament cytoskeleton are important in the development of compaction, which is crucial for establishment of trophoblast and pluriblast (inner cell mass) lineages and for subsequent development. Members of the Rho family of p21 GTPases have been shown to regulate the organisation of the actin cytoskeleton and adhesion in other cell types. The potential role of these proteins in compaction was investigated. Inhibition of Rho with Clostridium botulinum C3-transferase disturbed intercellular flattening at compaction and prevented cytocortical microfilament polarisation of eight-cell blastomeres, in contrast to cytochalasin D which inhibited only adhesion. Microinjection of a constitutively activated recombinant Rho protein into four-cell blastomeres induced cortical microfilament disruption and apical displacement of nuclei associated with polarised clustering of microtubules. Interblastomere adhesion was reduced and E-cadherin was aberrently clustered at remaining cell-cell contacts. Similarly, activated Cdc42 protein induced nuclear displacement with additional cytoplasmic actin bundle formation between nucleus and cell-cell contacts. The effects produced by both of the activated GTPase proteins are indicative of prematurely induced but aberrently organised polarity. These results suggest that Rho family GTPases are involved in the polarisation of early mouse blastomeres.
ADP Ribose Transferases↗
Are we using appropriate self-report questionnaires for detecting anxiety and depression in women with early breast cancer?
The aim of this prospective study was to identify the psychiatric morbidity associated with the diagnosis and treatment of early breast cancer. At each of five time points, 269 women were interviewed using a shortened version of the Present State Examination (PSE) and 266 completed self-assessment questionnaires, the Hospital and Anxiety Depression Scale (HADS) and the Rotterdam Symptom Checklist (RSCL). This paper compares the ability of the questionnaires to detect psychiatric morbidity with that of the PSE. The majority of women who experienced anxiety and/or depression did so within 3 months of their initial surgery. The clinical interview identified anxiety disorder in 132 of 266 women (49.6%) and depressive illness in 99/266 (37.2%) during the first 3 months. Using the recommended threshold of > or = 11 for caseness, the sensitivities for both tests were very low at 24.2% (HADS anxiety) and 14.1% (HADS depression) and 30.6% (RSCL psychological distress scale). Lowering the threshold value to > or = 7 on the HADS improved the sensitivity to 72% for the anxiety subscale, but it remained low at 37.4% for the depression subscale. A threshold of > or = 7 for the RSCL scale raised sensitivity to 66.7%. Lowering the threshold values raised the sensitivity of both the instruments but decreased their specificity: the lower the threshold, the greater the number of women who were identified as false positives which would increase the work load for clinic staff if used as a screening tool. Given that the HADS was inadequate in discriminating for depressive illness, it was not surprising that its use as a unitary scale with a threshold value as low as 12 resulted in a sensitivity of only 42.7%. In the light of these findings, we question the use of both the HADS and the RSCL as suitable research or screening instruments for detection of psychological morbidity in early breast cancer.
Adult↗