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Biomedical subjects

R Hopkins

Publications and source records attributed to R Hopkins.

At least 19 recordsLinked to original sources

Development and characterisation of human 5-HT1B- or 5-HT1D-receptor specific antibodies as unique research tools.

The serotonin 5-HT1B/1D-receptor family comprises of two closely related receptors encoded by two distinct genes. There are no pharmacological ligands which can adequately distinguish between these two receptor subtypes in human tissues. Therefore, we have developed human 5-HT1B- and 5-HT1D-receptor subtype specific polyclonal antibodies. Rabbits were immunised with synthetic peptides identical to unique amino acid sequences located in the third intracellular loops of these receptors. Polyclonal antibodies were subjected to immunoaffinity purification and were characterised using ELISA, dot blot analysis and immunostaining of stably-transfected CHO cell lines expressing either human 5-HT1B-receptors or 5-HT1D-receptors and in human trigeminal ganglia. The antibodies were specific for either the 5-HT1B- or 5-HT1D-receptors and did not cross-react. Both 5-HT1B- and 5-HT1D-immunoreactivities were detected on cell bodies in human trigeminal ganglia. In the absence of selective pharmacological agents, these antibodies represent unique and essential research tools to study the anatomical distribution of 5-HT1B/1D-receptor subtypes in human tissue.

Amino Acid Sequence

Individual cognitive-behavioural interventions in early psychosis.

BACKGROUND: Cognitive-behavioural treatments have previously been explored in the treatment of chronic psychotic problems, but recently, the effectiveness of these treatments has been investigated with regard to recent onset and acute psychosis. METHOD: The literature relating to cognitive-behavioural treatments in psychosis is explored and the application of the approach to recent onset psychosis is described in detail. RESULTS: There appears to be a growing body of evidence that the advances made in the treatment of people with chronic treatment resistant psychosis can be similarly applied to people with recent onset and acute psychosis. CONCLUSIONS: Cognitive-behavioural treatments are feasible with recent onset psychotic patients although further evaluation of their effectiveness is necessary.

Antipsychotic Agents

A comparison of the repetitive click and conditioning-testing P50 paradigms.

The auditory P50 ERP component has previously been studied either in the repetitive click or the conditioning-testing (C-T) paradigm. For 20 subjects, we compared 4 repetitive click and 4 C-T protocols in a single experimental session with identical recording techniques and with interclick intervals comparable to the C-T intervals. In the C-T protocols, a long interval between click pairs ensured full recovery of P50 to the C click. The analysis of P50 topographies provided strong evidence that the same component was measured in the two paradigms. For both paradigms, P50 amplitude was progressively suppressed as the interclick or C-T interval decreased (P < 0.0001), with parallel interval vs. P50 amplitude regression lines for the two paradigms. There was a strong trend (P = 0.08) for the repetitive click amplitudes to be smaller than T amplitudes for comparable repetitive click and C-T intervals. Equivalently, this strong trend suggests that repetitive click intervals must be longer (by about 300 ms) than the C-T interval to generate equivalent amplitude P50 responses. We conclude that the same component is measured in both paradigms, that P50 amplitude decreases with decreasing interstimulus intervals in both paradigms, and that in normals, for comparable inter-click and C-T intervals, there is greater P50 suppression in the repetitive click paradigm. Finally, we note that the comparison of paradigms within normals does not necessarily apply to clinical samples.

Acoustic Stimulation

Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs.

Sumatriptan, a 5HT1B/1D-receptor agonist, is clinically effective as an antimigraine agent. Its therapeutic action may result partly from vasoconstriction of excessively dilated cranial blood vessels (a 5HT1B-receptor mediated response). The antimigraine activity of sumatriptan may also result from inhibition of the release of vasoactive neuropeptides from trigeminal sensory fibres within the meninges. The identity of the 5HT1B/1D-receptor subtype mediating this effect is unknown. Using 5HT1D- and 5HT1B-receptor-specific antibodies we have demonstrated a differential distribution of these receptor subtypes within the human trigemino-cerebrovascular system. Only 5HT1B-receptor protein was detected on dural arteries. In contrast, only 5HT1D-receptor protein was detected on trigeminal sensory neurones including peripheral and central projections to dural blood vessels and to the medulla. Within the medulla 5HT1D-receptor protein was confined to discrete areas associated with the trigeminal sensory system. These findings have important implications for the design of new antimigraine drugs.

Adult

Outbreak of sporotrichosis among tree nursery workers.

In spring 1994, an outbreak of sporotrichosis occurred at a tree nursery in Florida; 9 (14%) of 65 workers involved in production of sphagnum moss topiaries developed lymphocutaneous sporotrichosis. A cohort study of all 65 employees was conducted to identify risk factors for sporotrichosis, and an environmental investigation was done. The risk of sporotrichosis increased significantly with the duration of working with sphagnum moss (P < .05), in particular with filling topiaries (P < .05), and with having less gardening experience (P < .05). Wearing gloves was protective (P < .005). Sporothrix schenckii was cultured from patients and sphagnum moss used in topiary production. Use of restriction fragment length polymorphism revealed an identical pattern for patient isolates that was different from the patterns of environmental isolates. Physicians should be aware of sporotrichosis in patients with ulcerative skin lesions who have a history of occupational or recreational exposure to sphagnum moss.

Adult

Mice deficient for the amyloid precursor protein gene.

To understand the in vivo function of the amyloid precursor protein (APP) we generated an APP null mutation in mice by homologous recombination in embryonic stem (ES) cells. We show here that homozygous APP deficient mice were produced at expected frequencies. Neither APP mRNA nor protein could be detected in these animals. Yet the homozygous APP mutant mice are fertile and do not show overt abnormalities at up to 12 weeks of age. Neuroanatomical studies of the brain did not reveal significant differences in the knockout mice as compared to the wild-type controls. These results argue against an essential function of APP in mouse embryonic and early neuronal development.

Amyloid beta-Protein Precursor

Which is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study.

OBJECTIVE: To compare the efficacy of sulfasalazine (SSZ) with its two moieties, 5-aminosalicylic acid (ASA) and sulfapyridine (SP), in patients with active ankylosing spondylitis (AS). METHODS: A 26-week randomized, observer-blinded, 2-center, controlled study of treatment with either SSZ, ASA, or SP was conducted in 90 patients with active AS. Patients were evaluated at baseline and at monthly intervals, using several clinical and laboratory measures of disease activity. A global assessment of treatment efficacy was made by both patients and observers at the end of the study period. RESULTS: There were no significant changes in any of the parameters of disease activity in the ASA treatment group. Levels of serum IgG, IgA, and IgM fell significantly during treatment with SP, but none of the other changes reached statistical significance. Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ, as did nocturnal spinal pain and overall spinal pain. Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment. CONCLUSION: SP appears to be the active moiety in AS, although there was a trend suggesting a better outcome in the SSZ group compared with the SP group, perhaps suggesting the importance of a common sulfonamide structure for efficacy.

Adolescent

Induction of c-fos mRNA in the arcuate nucleus of normal and mutant growth hormone-deficient mice by a synthetic non-peptidyl growth hormone secretagogue.

We have studied by in situ hybridization histochemistry the mRNA expression of the c-fos immediate early gene in the brains of wild type and dwarf(dw/dw) and little(lit/lit) mutant mice after systemic injections of the synthetic GH secretagogues GHRP-6 and L-163,191. Both GH secretagogues induced a marked c-fos mRNA expression in the arcuate-ventromedial hypothalamus (ARC-VMH) of both control and mutant mice indicating a possible action on growth hormone releasing hormone (GHRH) neurones in the ARC-VMH. Both dw/dw and lit/lit mice showed a 5-fold elevation in GHRH mRNA expression in the ARC-VMH compared with control animals under basal conditions. Since lit/lit mice have a reduced ability to secrete GH and lack a functional GHRH receptor while dw/dw mice lack both GH and presumably GHRH receptors, the GH-secretagogue-induced c-fos mRNA in the brain of these mutants are unlikely to be mediated by an indirect action of GH or a interaction of the synthetic GH-secretagogue with the GHRH receptor.

Animals

beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.

In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an APP-null mutation in mice. Homozygous APP-deficient mice were viable and fertile. However, the mutant animals weighed 15%-20% less than age-matched wild-type controls. Neurological evaluation showed that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function. In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation.

Amyloid beta-Protein Precursor

Nail biting in rheumatic diseases.

To ascertain if nail biting (usually considered a manifestation of emotional tension) was associated with fibromyalgia, 387 patients attending the Rheumatism Clinic at the Leeds General Infirmary were studied prospectively. Bitten nails appeared to be a feature of youth rather than of fibromyalgia. Patients with a full set of dentures were less likely to bite their nails than others, but it can and was done by 7%. Posing the question about nail biting worried several patients, indicating the wisdom of seeking ethical approval even for "noninvasive" studies.

Adult

Long-term effects of Hurricane Andrew: revisiting mental health indicators.

Two population-based surveys of South Dade County, Florida, were conducted after Hurricane Andrew to compare hurricane-related symptoms of mental distress and describe the impact of mental health outreach teams. Households were selected by three-stage cluster sampling and findings from the two surveys, 13 months apart, were compared. Response rates were 75 per cent and 84 per cent. The prevalence of symptoms of mental distress decreased over time. However, in the households contacted by the teams (25 per cent of sample), the prevalence of symptoms (50 per cent) did not differ from households not contacted (43 per cent). Households contacted by teams that reported symptoms were just as likely to have been referred for help by the teams (72 per cent) as those without symptoms (68 per cent). Households reporting symptoms were equally likely to get counselling regardless of whether the teams visited. Mental health teams had no significant impact on mental health symptoms or the use of mental health services. Alternative approaches to mental health outreach teams need to be explored.

Adaptation, Psychological

Evaluation of long-term community recovery from Hurricane Andrew: sources of assistance received by population sub-groups.

Two three-stage cluster surveys were conducted in South Dade County, Florida, 14 months apart, to assess recovery following Hurricane Andrew. Response rates were 75 per cent and 84 per cent. Sources of assistance used in recovery from Hurricane Andrew differed according to race, per capita income, ethnicity, and education. Reports of improved living situation post-hurricane were not associated with receiving relief assistance, but reports of a worse situation were associated with loss of income, being exploited, or job loss. The number of households reporting problems with crime and community violence doubled between the two surveys. Disaster relief efforts had less impact on subjective long-term recovery than did job or income loss or housing repair difficulties. Existing sources of assistance were used more often than specific post-hurricane relief resources. The demographic make-up of a community may determine which are the most effective means to inform them after a disaster and what sources of assistance may be useful.

Disasters

Marginal copper-restricted diets produce altered cardiac ultrastructure in the rat.

To determine if chronic ingestion of a diet containing a marginally low level of Cu could cause deleterious alterations in cardiac ultrastructure, male offspring were nursed by dams fed a diet containing either 6.7 or 2.8 mg Cu/kg from midgestation through lactation before weaning to the same diet. Conventional measures of Cu status, including growth, relative heart weight, tissue concentrations of Cu, ceruloplasmin activity, and tissue activity of Cu,Zn-superoxide dismutase (SOD) were similar in both dietary treatment groups at 5.5 months of age. However, significant increases in the number and volume of lipid droplets and an increased incidence of pathological abnormalities in mitochondria and basal laminae were observed in sections of hearts from rats chronically fed the diet containing 2.8 mg/kg Cu. Reduction of the dietary level of Cu from 2.8 to 1.3 mg/kg from 4 to 5.5 months of age caused significant reductions in the concentration of Cu in serum and liver, but Cu content, Cu,Zn-SOD activity, pathological scores, and morphometric parameters in hearts were not modified by the greater restriction of dietary Cu in adult rats. This study suggests that abnormalities in cardiac ultrastructure occurred in rats chronically fed diets marginally low in Cu, despite minimal changes in conventional biochemical indicators of Cu status.

Animals