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Biomedical subjects

J Wood

Publications and source records attributed to J Wood.

At least 163 records · Page 9Linked to original sources
PubMed1993

Simplifying the interface for everyone.

Electronic systems used within the home and in public places are increasingly sophisticated. Simplifying the interface between people and these complex systems is a major design challenge. User trials which highlight the needs of older people can result in interface design which performs well for a wide range of users. Three case studies are outlined as illustrations.

Journal Article↗
PubMed1993

The effects of iontophoretic clonidine on neurones in the rat superficial dorsal horn.

Clonidine and glutamate were applied by iontophoresis to cells in the superficial 3 laminae of the spinal cord in the anaesthetised rat. Only cells that were excited by glutamate (up to 150 nA) were studied. Some spontaneously active cells could be excited by clonidine (up to 100 nA). However, when applied to non-spontaneous cells, clonidine had no effect at any dose level. When ejected in a cyclic pattern alternating with glutamate ejection, clonidine powerfully amplified the response of many cells to the glutamate stimulus. This effect was seen only on cells with small-amplitude spikes and low-threshold (LT) receptive fields. The amplification was often sustained and could outlast the clonidine ejection by several minutes. Clonidine had a long-lasting inhibitory effect on the responses to glutamate of cells with high-threshold (HT) or wide-dynamic-range (WDR) receptive fields. Clonidine appeared to selectively decrease the responsiveness of WDR cells to noxious stimulation. It is suggested that an amplification of the response of LT cells to other excitatory inputs could contribute to the analgesic action of clonidine.

Animals↗
PubMed1993

Analysis of interferon-alpha 2 sequences in human genomic DNA.

We have analyzed the genomic DNA sequence corresponding to the human interferon-alpha 2 (IFN-alpha 2) gene locus. In human lymphoblastoid Namalwa cells, we have detected sequences corresponding to IFN-alpha 2b and -2c, while in human KG-1 cells both IFN-alpha 2a and -2b were present. However, in 100 independent IFN-alpha 2 clones derived from 20 unrelated Caucasian volunteers, we found only sequences corresponding to IFN-alpha 2b. Statistical analysis of this result suggests that the sequences corresponding to IFN-alpha 2a and -2c are either rare allelic variants of this gene, occurring in only a minority of the Caucasian population, or are restricted to transformed cell lines.

Amino Acid Sequence↗
PubMed1993

Pharmacological profile of valsartan: a potent, orally active, nonpeptide antagonist of the angiotensin II AT1-receptor subtype.

1. The pharmacological profile of valsartan, (S)-N-valeryl-N-([2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl)-vali ne, a potent, highly selective, and orally active antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2. Valsartan competed with [125I]-AII at its specific binding sites in rat aortic smooth muscle cell membranes (AT1-receptor subtype) with a Ki of 2.38 nM, but was about 30,000 times less active in human myometrial membranes (AT2-receptor subtype). 3. In rabbit aortic rings incubated for 5 min with valsartan, at concentrations of 2, 20 and 200 nM, the concentration-response curve of AII was displaced to the right and the maximum response was reduced by 33%, 36% and 40%, respectively. Prolongation of the incubation time with valsartan to 1 h or 3 h, further reduced the maximum response by 48% or 59% (after 20 nM) and by 59% or 60% (after 200 nM) respectively. After 3 h incubation an apparent pKb value of 9.26 was calculated. Contractions induced by noradrenaline, 5-hydroxytryptamine, or potassium chloride were not affected by valsartan. No agonistic effects were observed in the rabbit aorta at concentrations of valsartan up to 2 microM. 4. In bovine adrenal glomerulosa, valsartan inhibited AII-stimulated aldosterone release without affecting the maximum response (pA2 8.4). 5. In the pithed rat, oral administration of valsartan (10 mg kg-1) shifted the AII-induced pressor response curves to the right, without affecting responses induced by the electrical stimulation of the sympathetic outflow or by noradrenaline. Animals treated with valsartan 24 h before pithing also showed significant inhibition of the response to AII. 6. In conscious, two-kidney, one-clip renal hypertensive rats (2K1C), valsartan decreased blood pressure in a dose-dependent manner after single i.v. or oral administration. The respective ED30 values were 0.06 mg kg-1 (i.v.) and 1.4 mg kg-1 (p.o.). The antihypertensive effect lasted for at least 24 h after either route of administration. After repeated oral administration for 4 days (3 and 10 mg kg-1 daily), in 2K1C renal hypertensive rats, systolic blood pressure was consistently decreased, but heart rate was not significantly affected. 7. In conscious, normotensive, sodium-depleted marmosets, valsartan decreased mean arterial pressure, measured by telemetry, after oral doses of 1-30 mg kg-1. The hypotensive effect persisted up to 12 h after 3 and 10 mg kg-1 and up to 24 h after 30 mg kg-1. 8. In sodium-depleted marmosets, the hypotensive effect of valsartan lasted longer than that of losartan(DuP 753). In renal hypertensive rats, both agents had a similar duration (24 h), but a different onset of action (valsartan at 1 h, losartan between 2 h and 24 h).9. These results demonstrate that valsartan is a potent, specific, highly selective antagonist of AII at theAT1-receptor subtype and does not possess agonistic activity. Furthermore, it is an efficacious, orally active, blood pressure-lowering agent in conscious renal hypertensive rats and in conscious normotensive,sodium-depleted primates.

Angiotensin I↗
PubMed1993

Spectral analyses of activity of laryngeal and orofacial muscles in stutterers.

Previous studies have reported that the disfluent speech of stutterers is often associated with tremor in orofacial muscle systems. In the present report, spectral analyses of the amplitude envelopes of laryngeal and orofacial EMGs revealed that tremor-like oscillations of EMG activity, similar to those observed in orofacial muscles, are also present in laryngeal muscles during stuttered speech. Furthermore, tremor-like oscillations in orofacial and laryngeal muscles appear to be entrained in some subjects. It is speculated that autonomic systems may provide a mechanism whereby oscillations in different muscle groups may become entrained.

Adult↗
PubMed1993

Variants of the MMPI 2-7-8 code type: schizotypal correlates of high point 2, 7, or 8.

Our study sought to evaluate whether examination of the high-point scale among subjects with a 2-7-8 parent configuration on the MMPI could assist in the identification of individuals with schizotypal features. Additionally, this study compared male 2-7-8 subjects to female 2-7-8 subjects to determine whether gender mediates endorsement of items associated with these features. Subjects (N = 106) who produced a 2-7-8 parent profile were subdivided according to high point (2, 7, or 8), and the three subgroups were subsequently compared on other self-report measures associated with schizotypal attributes. Subgroup comparisons revealed that the High 8 and High 2 groups produced a pattern of responding consistent with schizotypal characteristics. In contrast, the at-risk status of the High 7 group appears doubtful. Comparisons based on gender generally revealed no differences among female and male 2-7-8 subjects.

Adolescent↗
PubMed1993

What lessons can be learned from animal model studies in viral heart disease?

Several well-defined coxsackievirus B3 (CVB3)-murine models of inflammatory heart disease are providing information about mechanisms which contribute to myocyte necrosis. Severity of disease induced and mechanisms responsible depend upon unresolved molecular activities of the viral genome, nonspecific defenses of the mouse at time of infection and immune responses of the mouse at the time of infection. Most important are the capabilities and directed responses of each mouse to infection which are determined by age and genetic background of the host. In addition to virus-induced contributions to tissue pathology during primary infection, persistence of viral genomes for week to months in some strains of mice forecast whether the acute disease will resolve or continue as chronic disease with sustained inflammatory reactions in the myocardium. Persistent infections can contribute to nascent cardiopathologic alterations by chronic induction of inflammatory events through expression of viral genes and altered expression of host genes during nonlytic infections. Products of these expressions include viral proteins and nonhomeostatic levels of cytokines and arachidonic acid cascade intermediates and final metabolites. Molecular mimicry via shared epitopes between virion capsid proteins and normal cell molecules/structures located on or within heart tissue cells may be the mechanism by which immune systems in certain strains of mice are persistently stimulated. The products of these immune responses, i.e. antibodies and cytotoxic T lymphocytes, may provide initial protection via termination of infection and virus clearance during acute disease but subsequently these autoreactive processes could contribute to chronic disease. The immune effector products (antibodies and T lymphocytes) have potential pro-inflammatory reactivities, capacity for exacerbating ongoing CVB3-induced disease and/or can induce disease in normal animals. In further support of the hypothesis that autoimmune reactions contribute to sustained inflammation of the heart, non-viral models of myocarditis have been developed. Cell constituents such as myosin and adenosine nucleotide translocator protein can induce cardiopathologic alterations in normal mice of strains known to develop CVB3-induced chronic disease. Thus host genetic background determines whether a mouse survives the initial infection, resolves the acute disease or inadvertently contributes to sustained inflammatory heart disease. Finally, shared epitopes among the enteroviruses may play a role in repeated episodes of disease during sequential infections by different serotypes.

Animals↗
PubMed1992

Synergistic interaction between the probucol phenoxyl radical and ascorbic acid in inhibiting the oxidation of low density lipoprotein.

Chain-breaking antioxidants such as butylated hydroxytoluene, alpha-tocopherol, and probucol have been shown to decrease markedly the oxidative modification of low density lipoprotein (LDL). Their mechanism of action appears to involve scavenging of LDL-lipid peroxyl radicals. The purpose of this study was to investigate the occurrence of radical reactions produced during oxidation of LDL and LDL-containing probucol initiated by lipoxygenase or copper. In addition, we have investigated the possibility of a synergistic interaction between ascorbate and probucol in inhibiting the oxidation of LDL. Incubation of LDL-containing probucol and lipoxygenase produced a composite electron spin resonance (ESR) spectrum due to the endogenous alpha-tocopheroxyl radical and probucol-derived phenoxyl radical. The spectral assignment was further verified by chemical oxidation of alpha-tocopherol and probucol. In the presence of ascorbic acid, these radicals in the LDL particle were reduced to their parent compounds with concomitant formation of the ascorbate radical. In both the peroxidation of linoleic acid and the copper-initiated peroxidation of LDL, the antioxidant activity of probucol was significantly increased by low (3-6 microM) concentrations of ascorbate. The probucol-dependent inhibition of LDL oxidation was enhanced in the presence of ascorbic acid. We conclude that the reaction between the phenoxyl radical of probucol and ascorbate results in a synergistic enhancement of the antioxidant capacity of these two compounds and speculate that such reactions could play a role in maintaining the antioxidant status of LDL during oxidative stress in vivo.

Analysis of Variance↗
PubMed1992

Fibrinogen genotype and risk of peripheral atherosclerosis.

There is conflicting evidence about the influence of fibrinogen genotype on plasma fibrinogen concentrations, and the relation between genotype and atherosclerotic disease has not been studied. In a population-based case-control study we aimed to find out whether certain fibrinogen genotypes are associated with an increased risk of peripheral atherosclerosis. 121 subjects with peripheral arterial disease and 126 healthy controls matched for age and sex were selected from a random population sample aged 55-74 years in the Edinburgh Artery Study. Mean fibrinogen concentrations were higher in cases than in controls (3.12 [95% confidence interval 2.99-3.26] vs 2.75 [2.64-2.85], p less than 0.001). A greater proportion of cases than controls were homozygous or heterozygous for an allele at the beta fibrinogen locus (4.2 kb allele, Bcl I digestion); the allele frequency was 0.197 in cases and 0.097 in controls (p less than 0.005). Extended haplotypes for 4.2 kb heterozygotes were also associated with an increased risk of peripheral arterial disease. However, haplotype had only a small effect on the association of plasma fibrinogen concentration with disease, and the relation of haplotype with disease was independent of age, sex, social class, smoking status, plasma fibrinogen, alcohol consumption, body mass index, and diabetes mellitus. We conclude that variation at the beta fibrinogen locus is associated with an increased risk of peripheral atherosclerosis. The influence is not mediated simply by way of increased fibrinogen concentrations but could be due to a structurally variant fibrinogen or linkage disequilibrium with a neighbouring gene.

Aged↗