Biomedical subjects
Publications and source records attributed to T Jackson.
Clathrin-coated vesicles transport proteins and membranes between intracellular compartments. Adaptor molecules determine vesicle specificity; recently, a third type of adaptor protein, AP3, has been identified and implicated in the biogenesis of endosomal and lysosome-related organelles.
Oxygen isotope measurements of carbonate from martian meteorite ALH 84001 (delta18O = 18.3 +/- 0.4 per mil, delta17O = 10.3 +/- 0.2 per mil, and Delta17O = 0.8 +/- 0.05 per mil) are fractionated with respect to those of silicate minerals. These measurements support the existence of two oxygen isotope reservoirs (the atmosphere and the silicate planet) on Mars at the time of carbonate growth. The cause of the atmospheric oxygen isotope anomaly may be exchange between CO2 and O(1D) produced by the photodecomposition of ozone. Atmospheric oxygen isotope compositions may be transferred to carbonate minerals by CO2-H2O exchange and mineral growth. A sink of 17O-depleted oxygen, as required by mass balance, may exist in the planetary regolith.
OBJECTIVE: This cross-sectional study evaluated the extent to which relations between employment status and emotional distress are mediated by pain-related and psychosocial measures among employed and unemployed persons with chronic pain. DESIGN: A total of 40 unemployed and 43 employed persons reporting chronic pain were recruited from pain services at a tertiary-care hospital and community-based organizations. Volunteers completed self-report measures of pain severity, subjective financial stress, time structure, emotional distress, and background data. RESULTS: A path analysis indicated that pain severity had direct associations with both emotional distress and employment status. In addition, employment status was only indirectly related to emotional distress; this relation was mediated by levels of reported financial strain and structured purposeful time use. CONCLUSIONS: Findings suggest that pain severity and the quality of specific experiences related to being employed or unemployed as opposed to employment status per se correspond directly to levels of emotional distress reported by some persons with chronic pain.
This study examined how illness schemata-ways people organize information about illness-change over the course of cognitive-behavioral treatment of chronic headache and the extent to which such changes predict reduction of headache. 73 subjects with chronic migraine, mixed migraine and tension, or tension headache were classified on the basis of outcome from imagery-based treatment as Treatment-responders (n = 24). Treatment nonresponders (n = 27), and Monitoring Controls (n = 22). Self-reported illness schemata related to the seriousness and changeability of headache were assessed at pretreatment and 8-wk. follow-up. While groups did not differ on pretreatment measures of illness schemata, at follow-up the Treatment responder group reported higher Changeability scores than Treatment-nonresponders and Control subjects and lower Seriousness scores than Control subjects. Headache reduction at follow-up was related to follow-up Changeability scores, in-session changes in systolic blood pressure and reported posttreatment expectations of headache activity, but not pretreatment measures of illness schemata. Findings indicate that improvements in headache activity are not influenced by the severity of headaches and may change prior to cognitive-behavioral treatment. Rather, among individuals who show decreases in headache activity, changes in beliefs about illness and headache reduction may have reciprocal relations both of which result from cognitive behavioral treatment.
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Haloperidol, used to treat patients with psychoses, is considered minimally cardiotoxic. Several cases of torsade de pointes have been reported in association with the use of oral haloperidol. In each of those cases, a prolonged QTc preceded the torsade de pointes episode and thus may be considered a predictor for ventricular arrhythmias in elderly women treated with haloperidol. However, the following case may demonstrate the inability to predict an episode of torsade de pointes with low-dose oral haloperidol use.
Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.
The standard Monod model for microbial population dynamics in the chemostat is modified to take into consideration that cells can adapt to the change of nutrient concentration in the chemostat by switching between fast and slow nutrient uptake and growing modes with asymmetric thresholds for transition from one mode to another. This is a generalization of a modified Monod model which considers adaptation by transition between active growing and quiescent cells. Global analysis of the model equations is obtained using the theory of asymptotically autonomous systems. Transient oscillatory population density and hysteresis growth pattern observed experimentally, which do not occur for the standard Monod model, can be explained by such adaptive mechanism of the cells. Competition between two species that can switch between fast and slow nutrient uptake and growing modes is also considered. It is shown that generically there is no coexistence steady state, and only one steady state, corresponding to the survival of at most one species in the chemostat, is a local attractor. Numerical simulations reproduce the qualitative feature of some experimental data which show that the population density of the winning species approaches a positive steady state via transient oscillations while that of the losing species approaches the zero steady state monotonically.
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Patients with mesial temporal lobe epilepsy (MTLE) have asymmetric hippocampal volumes with atrophy that sometimes by visual inspection appears to favor different regions along the longitudinal axis of the affected hippocampus. Histological studies suggest that cell loss may affect the anterior hippocampus preferentially, and that hippocampal sclerosis (HS) limited to the anterior of the hippocampus may indicate better surgical outcome. We used volumetric magnetic resonance imaging (MRI): (1) to objectively describe the distribution of volume loss in HS; and (2) to relate this distribution to outcome of temporal lobectomy. Hippocampal volumes and anterior and posterior subvolumes (AHV, PHV) were measured from MP-RAGE MRI in 43 temporal lobectomy patients with MTLE determined by pathological findings of HS and compared to 23 age-matched controls. Atrophy was defined as 'anterior', 'diffuse', 'posterior', or 'normal' depending on position of AHV and PHV relative to the mean +/- 2 S.D. of regional volumes of control hippocampi. Anterior to posterior ratios (APR = AHV/PHV) were also calculated. Mean APR of hippocampi ipsilateral to lobectomy cannot be distinguished from hippocampi contralateral to lobectomy or from controls. AHV and PHV from hippocampi contralateral to temporal lobectomy were smaller than controls but larger than hippocampi ipsilateral to lobectomy. Surgical outcome was independent of longitudinal distribution of atrophy. We determined that overall volume loss in HS is diffuse, neither clearly favoring the head nor body-tail. Surgical outcome for MTLE is not related to the longitudinal distribution of atrophy revealed by volumetric MRI.
This study examined the extent to which measures of psychosocial features of employment status predict emotional distress in chronic pain (n = 83) and healthy comparison (n = 88) samples. Participants completed measures of emotional distress, pain severity, psychosocial features of employment status, and demographic data. After controlling for length of current unemployment, number of pain sites, and level of current pain severity, psychosocial measures (structured and purposeful time use, perceived financial security, skill use, social support form formal sources) were significant predictors of emotional distress in the chronic pain sample. Similar results were obtained for the healthy comparison sample. Structured and purposeful time use emerged as the most significant individual predictor of emotional distress for both samples. Findings are discussed in terms of their potential implications for treating chronic pain patients and the need to develop multidimensional measures that assess features of employment status within chronic pain samples.
Policy-makers have always found it problematic to formulate fair and consistent counting rules for public hospital outpatient activities. In the context of output-based funding, such rules have consequences which can affect patient care. This paper reviews the rationale for organising multidisciplinary clinics and reports on a series of focus groups convened in four Melbourne teaching hospitals to consider funding policy for such clinics. It discusses issues of targeting outpatient services, along with implications for payment policy. It evaluates counting rules in terms of intended and unintended consequences in the context of Victoria's introduction of output-based funding for outpatient services.
UNLABELLED: Occlusion of the internal carotid artery (ICA) results in acute cerebral hypotension. We hypothesized that during acute cerebral hypotension, in addition to physiological autoregulation, further arteriolar relaxation is possible by pharmacological means. We tested the feasibility of using intracarotid verapamil, a calcium channel blocker, to decrease the cerebrovascular resistance (CVR) and augment cerebral blood flow (CBF) at low postocclusion distal ICA pressures (PICA). Eleven patients undergoing trial occlusion of ICA were enrolled. Distal ICA or stump pressure, hemispheric CBF, and CVR were determined before and after carotid occlusion. During ICA occlusion, CBF and other physiological variables were determined before and after intracarotid verapamil. Two patients were excluded from the study. Carotid occlusion (n = 9) significantly decreased PICA (mean +/- SD, from 82 +/- 22 to 46 +/- 11 mm Hg, P = 0.001) and CBF (from 42 +/- 11 to 33 +/- 11 mL.100 g-1.min-1, P < 0.05). During occlusion, after intracarotid verapamil (3.9 +/- 1.6 mg), hemispheric CBF tended to increase from 31 +/- 11 to 35 +/- 14 mL.100 g-1.min-1 (P = 0.067). However, the percent increase in CBF after verapamil was a linear function of PICA (y = 1.01 x -32, n = 9, r2 = 0.84, P = 0.006). The decrease in CBF during carotid occlusion suggests that near maximal cerebral autoregulatory vasodilation had occurred, although our results indicate that it may be feasible to further augment CBF by pharmacological means during acute cerebral hypotension. IMPLICATIONS: When the internal carotid artery is occluded during neurosurgical procedures, there may be a significant reduction in cerebral perfusion. The authors have demonstrated that the intraarterial administration of verapamil increases cerebral blood flow as a linear function of cerebral artery pressure. Intracarotid injection of vasodilators may augment cerebral blood flow during acute cerebral hypotension.
PURPOSE: We measured absolute volumes and volume differences of hippocampi in patients with mesial temporal lobe epilepsy (MTLE) using volumetric magnetic resonance imaging (MRI) to determine the extent of bilateral atrophy in MTLE and to relate hippocampal volumes (HV) to outcome of temporal lobectomy. METHODS: HV and hippocampal differences (HD) were measured in 40 patients with MTLE determined by pathology of hippocampal sclerosis (HS) and compared with those of age-matched controls. Results were matched with surgical outcome. RESULTS: Hippocampi contralateral to lobectomy (right hippocampi 2.96 +/- 0.49 cm3, left 3.14 +/- 0.51 cm3) were significantly smaller than those of controls (right hippocampi 3.73 +/- 0.52 cm3, left 3.60 +/- 0.51 cm3) but were significantly larger than hippocampi ipsilateral to lobectomy (right hippocampi 2.63 +/- 0.61 cm3, 2.18 cm3) as compared across groups by analysis of variance (ANOVA: F = 27.2, p < 0.0001). The smaller hippocampus was ipsilateral to lobectomy in 39 of 40 cases. Seven of 40 MTLE patients (18%) had bilateral atrophy, defined by volumes of each hippocampi 2 SD lower than control means. Surgical outcome was independent of hippocampal asymmetry and bilateral atrophy measured by chi-square and Fisher's exact tests. CONCLUSIONS: We determined that most patients with MTLE have some degree of bilateral, asymmetric hippocampal pathology. However, asymmetry and bilateral atrophy have no clear relation to surgical outcome.
The integrin alpha(v)beta3 has been shown to act as the receptor for internalization of foot-and-mouth disease virus (FMDV) (A12), with attachment being through a highly conserved RGD motif located on the G-H loop of viral capsid protein VP1. In addition, however, we have recently shown that efficient infection of culture-grown cells by FMDV (O1BFS) requires binding to cell surface heparan sulfate. In this study, we have used a solid-phase receptor binding assay to characterize the binding by FMDV to purified alpha(v)beta3 in the absence of heparan sulfate and other cell surface components. In this assay, FMDV (O1BFS) successfully replicated authentic ligand binding by cellular alpha(v)beta3 in terms of its high affinity, dependence on divalent cations, and activation by manganese ions. Virus binding to this preparation of alpha(v)beta3 was exquisitely sensitive to competition by short RGD-containing peptides (50% inhibition at < 10(-8) M peptide), and this inhibition was highly sequence specific, with the equivalent RGE peptide being at least 10(4) fold less effective as a competitor. Representative viruses of the other six serotypes of FMDV bound to alpha(v)beta3 in a similar RGD-specific manner, although significant differences in sensitivity to RGD peptides suggest that the affinity of the different FMDV serotypes for alpha(v)beta3 is influenced, in part, by the variable amino acid residues in the VP1 G-H loop on either side of the RGD.
Empty capsids of foot-and-mouth disease virus (FMDV) type A22 Iraq 24/64, whose structure has been solved by X-ray crystallography, are unusual for picornaviruses since they contain VP2 and VP4, the cleavage products of the protein precursor VP0. Both the N terminus of VP1 and the C terminus of VP4, which pack together close to the icosahedral threefold symmetry axis where three pentamers associate, are more disordered in the empty capsid than they are in the RNA-containing virus. The ordering of these termini in the presence of RNA strengthens interactions within a single protomer and between protomers belonging to different pentamers. The disorder in the FMDV empty capsid forms a subset of that seen in the poliovirus empty capsid, which has VP0 intact. Thus, VP0 cleavage confers stability on the picornavirus capsid over and above that attributable to RNA encapsidation. In both FMDV and poliovirus empty capsids, the internal disordering uncovers a conserved histidine which has been proposed to be involved in the cleavage of VP0. A comparison of the putative active sites in FMDV and poliovirus suggests a structural explanation for the sequence specificity of the cleavage reaction.
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Nitric oxide (NO) and superoxide are both constitutive products of the endothelium. Because NO is readily inactivated by superoxide, the bioactivity of endothelium-derived NO (EDNO) is dependent on local activity of superoxide dismutase (SOD). We examined the effects of chronic inhibition of copper-zinc SOD (CuZnSOD) using a rat model of dietary copper restriction. Male weanling Sprague-Dawley rats were fed a Cu-deficient diet and received either no Cu replacement (Cu-deficient) or Cu in the drinking water (Cu-sufficient). Compared with Cu-sufficient animals, Cu-deficiency was associated with a 68% reduction in CuZnSOD activity and a 58% increase in vascular superoxide as estimated by lucigenin chemiluminescence (both P < .05). Compared with Cu-sufficient animals, arterial relaxation in the thoracic aorta from Cu-deficient animals was 10-fold less sensitive to acetylcholine, a receptor-dependent EDNO agonist, but only 1.5-fold less sensitive to A23187, a receptor-independent EDNO agonist, and only 1.25-fold less sensitive to authentic NO (all P < .05). In contrast, acute inhibition of CuZnSOD with 10 mM diethyldithiocarbamate produced a more uniform reduction in sensitivity to acetylcholine (8-fold), A23187 (10-fold), and NO (4-fold; all P < .001). Cu-deficient animals demonstrated a 2.5-fold increase in plasma-esterified F2-isoprostanes, a stable marker of lipid peroxidation, that correlated inversely with arterial relaxation to acetylcholine (R = -.83; P < .0009) but not A23187 or authentic NO. From these findings, we conclude that chronic inhibition of CuZnSOD inhibits EDNO-mediated arterial relaxation through two mechanisms, one being direct inactivation of NO and the other being lipid peroxidation that preferentially interrupts receptor-mediated stimulation of EDNO.