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Biomedical subjects

T Jackson

Publications and source records attributed to T Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus.

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.

Aphthovirus↗
PubMed1997

Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation.

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.

Acetylcholine↗
PubMed1997

Intra-arterial nitrovasodilators do not increase cerebral blood flow in angiographically normal territories of arteriovenous malformation patients.

BACKGROUND AND PURPOSE: The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs. METHODS: CBF was measured using the superselective intra-arterial 133Xe method before and after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n = 16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). RESULTS: Mean +/- SD systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (r = .57, P = .0051). CONCLUSIONS: When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide-mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.

Acetylcholine↗
PubMed1997

The relationship between length of vocational disability, psychiatric illness, life stressors and sociodemographic variables.

OBJECTIVE: The primary objective of this study was to examine the relationship between vocational disability, psychiatric illness, life stressors and sociodemographic factors. METHOD: Information on a variety of variables was obtained from insurance files of 147 subjects who had submitted claims for monetary compensation on grounds of psychiatric symptoms. RESULTS: The majority of subjects received a diagnosis of mood disorder or anxiety disorder. Extended vocational disability was associated with longer duration of psychiatric illness, rating of poorer prognosis by the treating physician, and lower income and occupational levels. Individuals with recent onset of disability reported more stressors than those experiencing extended disability. CONCLUSION: Although longer duration of psychiatric illness was associated with vocational disability, other variables play an important role in accounting for extended vocational disability.

Adult↗
PubMed1996

Perturbations in the surface structure of A22 Iraq foot-and-mouth disease virus accompanying coupled changes in host cell specificity and antigenicity.

BACKGROUND: Foot-and-mouth disease virus (FMDV) is an extremely infectious and antigenically diverse picornavirus of cloven-hoofed animals. Strains of the A22 subtype have been reported to change antigenically when adapted to different growth conditions. To investigate the structural basis of this phenomenon we have determined the structures of two variants of an A22 virus. RESULTS: The structures of monolayer- and suspension-cell-adapted A22 FMDV have been determined by X-ray crystallography. Picornaviruses comprise four capsid proteins, VP1-4. The major antigenic loop of the capsid protein VP1 is flexible in both variants of the A22 subtype but its overall disposition is distinct from that observed in other FMDV serotypes (O and C). A detailed structural comparison between A22 FMDV and a type O virus suggests that different conformations in a portion of the major antigenic loop of VP1 (the GH loop, which is also central to receptor attachment) result in distinct folds of the adjacent VP3 GH loop. Also, a single mutation (Glu82-->Gly) on the surface of VP2 in the suspension-cell-adapted virus appears to perturb the structure of the VP1 GH loop. CONCLUSION: The GH loop of VP1 is flexible in three serotypes of FMDV, suggesting that flexibility is important in both antigenic variability and structural communication with other regions of the virus capsid. Our results illustrate two instances of the propagation of structural perturbations across the virion surface: the change in the VP3 GH loop caused by the VP1 GH loop and the Glu82-->Gly change in VP2 which we believe perturbs the GH loop of VP1. In the latter case, the amplification of the sequence changes leads to differences, between the monolayer- and suspension-cell-adapted viruses, in host-cell interactions and antigenicity.

Antigens, Viral↗
PubMed1996

Gyral morphology in the posterior Sylvian region in families affected by developmental language disorder.

This study describes the family aggregation of gyral morphology in the posterior perisylvian region in families that contain one or more children with a developmental language disorder. The probands in these families were 8 male and 2 female children referred through therapy programs and schools for children with language and reading problems. Family members included both biological parents (10 m, 10 f) and all available siblings (6 m, 4 f). Gyral morphology in the members of these families was compared with control subjects (10 m, 10 f) who were without a personal or family history of developmental language disorders. Gyral morphology was evaluated using T1-weighted sagittal scans from a GE Signa 1.5T magnet, 5 mm consecutive slices through the full brain volume. A less common type of Sylvian fissure morphology was more frequently found in the hemispheres of language-disordered subjects and their first-degree relatives than in control subjects. In addition, the pattern of Sylvian fissure morphology across generations within the families suggests that this feature might be inherited from either parent. The elevated rate of extra gyri in the posterior perisylvian region in families affected by language disorder links an anomaly within a language-related brain region with familial risk for this disorder.

Adult↗
PubMed1996

NIST SRM 1945, whale blubber, NIST SRM 1974a, organics in mussel tissue, and NIST SRM 1941a, organics in marine sediment as certified reference materials for polychlorinated dioxins and furans in marine ecosystems.

Few natural matrix Standard Reference Materials are available for the validation of analytical methods measuring polychlorinated dioxins and furans (PCDDs and PCDFs) in marine ecosystems. The concentrations of PCDDs and PCDFs in NIST SRM 1945, SRM 1974a, and SRM 1941a are of interest because the analysis of marine mammal, mussel tissues and sediments have become important tools in the determination of organochlorine contamination of the environment. Because these SRMs have been demonstrated to be homogenous for other organic contaminants, they would be expected to be reliable standards for validation of polychlorinated dioxins and furans in marine mammals, mussels and sediments as well.

Animals↗
PubMed1996

A proposal for managed care payment options for patients with chronic conditions.

This paper proposes an episode of care payment system for patients with chronic illnesses, extending earlier published work on this model of ambulatory care (Duckett and Jackson 1993). The payment system relies on annual voluntary enrollment and some marginal broadening of Medicare coverage in exchange for patients' willingness to participate in an ambulatory managed care arrangement. In the context of Australian health ministers' enthusiasm for managed care, the proposal embodies an intermediate policy approach which supports greater health care efficiency while minimising the prospect for reductions in patient autonomy or serious distortions in patterns of care. The policy is not designed to be applied population-wide, but to address the issues involved with a resource-intensive patient group, those requiring ongoing management of chronic conditions.

Accreditation↗
PubMed1996

Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate.

Foot-and-mouth disease virus (FMDV) enters cells by attaching to cellular receptor molecules of the integrin family, one of which has been identified as the RGD-binding integrin alpha(v)beta3. Here we report that, in addition to an integrin binding site, type O strains of FMDV share with natural ligands of alpha(v)beta3 (i.e., vitronectin and fibronectin) a specific affinity for heparin and that binding to the cellular form of this sulfated glycan, heparan sulfate, is required for efficient infection of cells in culture. Binding of the virus to paraformaldehyde-fixed cells was powerfully inhibited by agents such as heparin, that compete with heparan sulfate or by agents that compete for heparan sulfate (platelet factor 4) or that inactivate it (heparinase). Neither chondroitin sulfate, a structurally related component of the extracellular matrix, nor dextran sulfate appreciably inhibited binding. The functional importance of heparan sulfate binding was demonstrated by the facts that (i) infection of live cells by FMDV could also be blocked specifically by heparin, albeit at a much higher concentration of inhibitor; (ii) pretreatment of cells with heparinase reduced the number of plaques formed compared with that for untreated cells; and (iii) mutant cell lines deficient in heparan sulfate expression were unable to support plaque formation by FMDV, even though they remained equally susceptible to another picornavirus, bovine enterovirus. The results show that entry of type O FMDV into cells is a complex process and suggest that the initial contact with the cell surface is made through heparan sulfate.

Animals↗
PubMed1996

The differential effects of employment status on chronic pain and healthy comparison groups.

We evaluated the differential effects of employment status on chronic pain and healthy comparison groups. Forty unemployed and 43 employed individuals with chronic pain, as well as 43 unemployed and 45 employed healthy comparison participants completed a series of measures assessing background information physical and psychological adjustment, and psychosocial features of employment status. In general, participants experiencing both chronic pain and unemployment reported poorer adjustment than the other groups and more financial strain, less structured and purposeful activity, fewer opportunities for skill use and task variety, and decreased social support than the employed chronic pain and healthy comparison groups. Groups did not differ, however, in work ethic values. Scores on measures of pain severity and features of employment status accurately predicted the group membership of more than 70% of respondents from four groups. The study suggests that there is utility in understanding experiences of chronic pain patients on the basis of features of their current employment status and points to a need for multidimensional measures that evaluate psychosocial facets of employment and unemployment specifically for chronic pain samples.

Journal Article↗
PubMed1995

Structural comparison of two strains of foot-and-mouth disease virus subtype O1 and a laboratory antigenic variant, G67.

BACKGROUND: Foot-and-mouth disease viruses (FMDVs) are members of the picornavirus family and cause an economically important disease of cloven-hoofed animals. To understand the structural basis of antigenic variation in FMDV, we have determined the structures of two viruses closely related to strain O1BFS whose structure is known. RESULTS: The two new structure are, like O1BFS, both serotype O viruses. The first, O1 Kaüfbeuren (O1K), is a field isolate dating from an outbreak of FMD in Europe in the 1960s. The second, called G67, is a quadruple mutant of O1K, generated in the laboratory, that bears point mutations conferring resistance to neutralizing by monoclonal antibodies, specific for each of the four major antigenic sites defined previously. The availability of the three related virus structures permits a detailed analysis of the way amino acid substitutions influence antigenicity. Structural changes are seen to be limited, in general, to the substituted side chain. For example, the GH loop of VP1, a highly antigenic and mobile protuberance which becomes ordered only under reducing conditions, was essentially indistinguishable in the three viruses despite the accumulation of up to four changes within its 15-residue sequence. At one of the other antigenic sites, however, changes between the two field strains did perturb both side-chain and main-chain structures in the vicinity. CONCLUSIONS: The conservation of conformation of the GH loop of VP1 adds to the evidence implicating an integrin as the cellular receptor for FMDV, since this loop contains a conserved RGD (Arg-Gly-Asp) sequence structurally similar to the same tripeptide in some other integrin-binding proteins. Structural changes required for the virus to escape neutralization by monoclonal antibodies are generally small. The more extensive type of structural change exhibited by the field isolates probably reflects differing selective pressures operating in vivo and in vitro.

Amino Acid Sequence↗
PubMed1995

Serum thyrotropin in primary hypothyroidism. A possible predictor of optimal daily levothyroxine dose in primary hypothyroidism.

BACKGROUND: Pretreatment thyrotropin levels may be a reliable predictor of the optimal daily dose of levothyroxine sodium in patients with primary hypothyroidism. However, the older method of serum thyrotropin determination, with the reference range of less than 1 to 8 mU/L, has given way to a newer, supersensitive thyrotropin assay, with a reference range of 0.5 to 5.0 mU/L. Thus, at present, the previously established relationship between the levothyroxine dose and the pretreatment serum thyrotropin concentration may not be reliable in predicting the optimal daily dose of levothyroxine. METHODS: We reassessed the relationship between the optimal daily levothyroxine dose and the pretreatment serum thyrotropin concentration as determined by the newer assay in 192 consecutive patients with primary hypothyroidism referred to an endocrinology clinic over a period of 4 years. RESULTS: The optimal daily dose of levothyroxine sodium ranged from 25 to 225 micrograms, with most patients (65%) requiring 100 to 150 micrograms/d and a median dose of 125 micrograms. Multiple regression analysis documented a significant curvilinear correlation between the mean pretreatment serum thryrotropin concentration and the optimal daily levothyroxine dose for individual groups divided according to available tablet strengths (r = .994, P < .001). A simple linear regression was also significant (r = .92, P < .001), although with an intercept much higher than the minimum levothyroxine sodium dose of 25 micrograms/d. However, the relationships markedly improved when the linear regressions were determined separately for two further subgroups at the median daily dose of 125 micrograms, providing equations to predict even the smallest optimal daily dose of levothyroxine. CONCLUSION: Pretreatment thyrotropin levels determined by new assays may also provide a useful guideline in determining the optimal daily maintenance dose of levothyroxine in patients with primary hypothyroidism.

Adult↗
PubMed1995

The relationship of various measures of time urgency to indices of physical health.

The degree of association with two general health indices was assessed for three separate measures of time urgency. The Speed and Impatience subscale of the Jenkins Activity Survey was found to have no significant relationships with the health indices. The Time Urgency/Perpetual Activation (TUPA) scale, as well as the Irritability and Impatience scale, did correlate in comparable ways with a majority of the health indicators. A very brief, 2-item impatience subscale of the Irritability and Impatience Scale also correlated with health indices in essentially the same manner as the complete Irritability and Impatience Scale and the TUPA Scale. It was concluded that because of its convenience of administration, the very brief 2-item impatience subscale of the Irritability and Impatience Scale may constitute the instrument of choice for assessing time urgency as it relates to noncardiovascular health. A question is raised regarding whether anger and time urgency constitute separate factors or are aspects of a single behavioral trait.

Adolescent↗
PubMed1995

Cost-effectiveness of laser ablation of the prostate. Premature evaluation.

A cost-effectiveness study compared visual laser ablation of the prostate (VLAP) with transurethral resection (TURP). Achieving equivalent outcomes, VLAP was more expensive than TURP. The result was sensitive to various assumptions, suggesting that VLAP might prove to be the preferred technology. Problems inherent in economic evaluation of emerging technologies are discussed.

Aged↗
PubMed1995

Dietary probucol preserves endothelial function in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation.

Excess vascular oxidative stress and the local formation of oxidized LDL (ox-LDL) have been implicated in the development of impaired endothelium-dependent arterial relaxation in hypercholesterolemia and atherosclerosis. Dietary antioxidants limit LDL oxidation in vitro and treatment of cholesterol-fed rabbits with dietary antioxidants preserves endothelium-derived relaxing factor (EDRF) action. To investigate the mechanism(s) responsible for these observations, we examined EDRF action, vascular oxidative stress, and antioxidant protection in male New Zealand White rabbits using four dietary treatments. Animals consumed standard chow (chow group) or chow supplemented with: (a) 0.5% cholesterol (0.5% cholesterol group); (b) 1% cholesterol (1% cholesterol group); or (c) 1% cholesterol and 1% probucol (probucol group). After 28 d of dietary treatment, segments of thoracic aorta from the 0.5 and 1% cholesterol groups demonstrated impairment of acetylcholine-mediated endothelium-dependent arterial relaxation compared to chow-fed animals (57 +/- 11% and 45 +/- 9% vs 78 +/- 3%, respectively; P < 0.05). In contrast, vessels from the probucol group demonstrated normal relaxation to acetylcholine (83 +/- 5%). Plasma cholesterol levels and the extent of atherosclerosis were similar among all cholesterol-fed groups. Probucol treatment was associated a threefold increase in LDL resistance to copper-induced oxidative modification (P < 0.05) and a reduction in tissue lipid peroxidation (as assessed by thiobarbituric acid-reactive substances; P < 0.05) compared to animals fed cholesterol alone. Most importantly, both of these changes were strongly correlated with preserved EDRF action. Moreover, cholesterol feeding was associated with a dose-dependent increase in vascular superoxide generation and lysophosphatidylcholine content, both of which were prevented by probucol treatment. From these findings, we conclude that probucol, a lipid-soluble antioxidant, preserves EDRF action in cholesterol-fed rabbits in association with limiting vascular oxidative stress and superoxide generation.

Animals↗