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Biomedical subjects

J Herron

Publications and source records attributed to J Herron.

At least 19 recordsLinked to original sources

A study of novel polymorphisms in the upstream region of vasoactive intestinal peptide receptor type 2 gene in autism.

We investigated the vasoactive intestinal peptide receptor type 2 (VIPR2) gene as a candidate gene for autism. We searched for mutations in the VIPR2 gene in autistic individuals, and 10 novel polymorphisms were identified. Three polymorphisms in the upstream region were studied in detail, and there was no significant difference in the frequencies between the autistic group (n = 14) and unrelated controls (n = 52). The distribution of the genotypes in two of the three polymorphisms differed somewhat between autistic subjects with gastrointestinal problems and those without. Moreover, there was a trend showing a correlation between the genotypes for the third polymorphism and the severity of stereotypical behavior as ranked by the Gilliam Autism Rating Scale. These preliminary results suggest that VIPR2 may have a role in gastrointestinal symptoms and stereotypical behaviors in autism, although a larger collection of samples suitable for transmission disequilibrium tests is necessary to validate the results.

Autistic Disorder↗

Adverse outcomes in a controlled trial of pergolide for cocaine dependence.

We conducted a double-blind, multiple dose comparison study of pergolide versus placebo for the treatment of cocaine dependence. In the present study, we examined patients who met criteria for cocaine dependence without comorbid alcohol dependence (N = 255). Study completion rates favored placebo (48.9%) over the low dose (33.3%) and high dose (21.5%) pergolide subjects (chi2(2) = 14.17, p < or = 0.001). Treatment effectiveness scores (TES) were significantly higher for the placebo group (31.7) than the low dose (25.2) and high dose (14.2) pergolide groups (F2,252 = 6.21, p = 0.002). There were no significant differences in side effect profiles after first dose of pergolide or placebo, or at study termination. Results of this study suggest that pergolide was not efficacious in the treatment of cocaine dependence due to reduced study participation. Caution regarding the outpatient use of pergolide in similar populations is warranted.

Adolescent↗

Attitudes toward suicide prevention in front-line health staff.

A questionnaire assessing attitudes toward suicide prevention was constructed and shown to have satisfactory reliability and internal consistency. The determinants and distribution of these attitudes were investigated in four groups of health professionals who are in contact with suicidal patients: general practitioners, accident and emergency nurses, psychiatrists in training, and community psychiatric nurses. Attitudes toward suicide prevention were shown to differ significantly between professional groups. More positive attitudes were associated with mental health professionals, working in the community, and previous training in suicide risk assessment. Negative attitudes should be assessed and targeted in training designed to improve the management of suicide risk.

Analysis of Variance↗

A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence.

Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population (N=358) and a per protocol population (N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.

Adolescent↗

Force probe measurements of antibody-antigen interactions.

The surface force apparatus has been used to quantify directly the forces that govern the interactions between proteins and ligands. In this work, we describe the measured interactions between the antigen fluorescein and the Fab' fragment of the monoclonal 4-4-20 anti-fluorescyl IgG antibody. Here we first describe the use of the surface force apparatus to demonstrate directly the impact of the charge composition in the region of the antibody binding site on the antibody interactions. Several approaches are described for immobilizing antigens, antibodies, and proteins in general for direct force measurements. The measured force profiles presented are accompanied by an extensive discussion of protocols used to analyze the force-distance curves and to interpret them in terms of the antibody structure. In addition to long-range electrostatic forces, we also consider short-range forces that can affect the strength of adhesion between the Fab' and immobilized fluorescein. The latter investigations demonstrate the influence of interfacial properties on the recognition of surface-bound antigens.

Antibodies, Monoclonal↗

Intra-cranial manifestations of the neurocutaneous syndromes.

The neurocutaneous syndromes or phakomatoses are a heterogeneous group of congenital disorders primarily involving structures derived from the embryological neuroectoderm. All of the syndromes involve the central nervous system (CNS). Peripheral nerves, skin and other organ systems may also be involved. Twenty to 30 disorders are now classified as neurocutaneous syndromes. This article reviews the intra-cranial imaging features of some of the commonest.

Adolescent↗

Voltage-gated K(+)-channel activity in ovine pulmonary vasculature is developmentally regulated.

To examine mechanisms underlying developmental changes in pulmonary vascular tone, we tested the hypotheses that 1) maturation-related changes in the ability of the pulmonary vasculature to respond to hypoxia are intrinsic to the pulmonary artery (PA) smooth muscle cells (SMCs); 2) voltage-gated K(+) (K(v))-channel activity increases with maturation; and 3) O(2)-sensitive Kv2.1 channel expression and message increase with maturation. To confirm that maturational differences are intrinsic to PASMCs, we used fluorescence microscopy to study the effect of acute hypoxia on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in SMCs isolated from adult and fetal PAs. Although PASMCs from both fetal and adult circulations were able to sense an acute decrease in O(2) tension, acute hypoxia induced a more rapid and greater change in [Ca(2+)](i) in magnitude in PASMCs from adult compared with fetal PAs. To determine developmental changes in K(v)-channel activity, the effects of the K(+)-channel antagonist 4-aminopyridine (4-AP) were studied on fetal and adult PASMC [Ca(2+)](i). 4-AP (1 mM) caused PASMC [Ca(2+)](i) to increase by 94 +/- 22% in the fetus and 303 +/- 46% in the adult. K(v)-channel expression and mRNA levels in distal pulmonary arteries from fetal, neonatal, and adult sheep were determined through the use of immunoblotting and semiquantitative RT-PCR. Both Kv2.1-channel protein and mRNA expression in distal pulmonary vasculature increased with maturation. We conclude that there are maturation-dependent changes in PASMC O(2) sensing that may render the adult PASMCs more responsive to acute hypoxia.

4-Aminopyridine↗

4-4-20 anti-fluorescyl IgG Fab' recognition of membrane bound hapten: direct evidence for the role of protein and interfacial structure.

The surface forces apparatus was used to identify the molecular forces that control the interactions of monoclonal 4-4-20 antifluorescyl IgG Fab' fragments with fluorescein-presenting supported planar bilayers. At long range, the electrostatic force between oriented Fab' and fluorescein monolayers was controlled by the composition of the protein exterior surrounding the antigen-combining site rather than by the overall protein charge. The measured positive electrostatic potential of the Fab' monolayer at pH > pI(Fab') was consistent with the structure of the exposed Fab' surface in which a ring of positive charge at the mouth of the antigen-combining site dominates the local electrostatic surface properties. Substantial differences in the electrostatic forces measured with denatured Fab' further demonstrated that the measured electrostatic surface properties and the consequent long-range interaction forces are controlled by the protein surface composition. At short range, the strength of the Fab'-mediated adhesion was modulated not only by the length of the fluorescein tether but also by membrane hydration. Steric hydration barriers at the membrane surface reduced the adhesion strength in proportion to their range of influence. These results provide direct evidence that long-range protein interactions with immobilized ligands are controlled by both the protein and the membrane surface compositions, while short-range, specific binding is modulated by both the protein structure and the membrane interfacial properties.

Antibodies, Monoclonal↗

Lower dose diuretic therapy in the treatment of patients with mild to moderate hypertension.

Indapamide (Lozol), an indoline antihypertensive drug with diuretic and vasodilating activities, was evaluated in 195 patients with mild to moderate essential hypertension (sitting DBP between 95 and 110 mmHg) in a multicentre, randomised, double-blind, parallel-group design trial. A four week single-blind placebo wash-out period was followed by an eight week double-blind period. Patients were randomised to indapamide 1.25 mg/day or to placebo. The primary efficacy endpoint was the mean change in sitting DBP from baseline to week 8. Ninety patients in the placebo group (93%) and 82 patients (84%) in the indapamide group completed the eight weeks of double-blind therapy. Indapamide produced a mean (SE) decrease in sitting DBP of 7.4 (0.63) mmHg (from 100.1 to 92.8 mmHg) compared with a decrease of 3.6 (0.75) mmHg (from 99.6 to 95.8 mmHg) produced by placebo (p < 0.0001). Indapamide and placebo also produced mean decreases in standing DBP of 6.8 (0.75) and 2.8 (0.77) mmHg, respectively (p = 0.0002), in sitting SBP of 11.1 (1.18) and 3.2 (1.35) mmHg, respectively (p = 0.0001) and in standing SBP of 11.4 (1.29) and 4.0 (1.43) mmHg, respectively (P = 0.0002). Reduction in BP of > or = 10 mmHg or to a DBP of < or = 90 mmHg was more frequent (P = 0.0005) among indapamide (46.6%) compared with placebo (23.7%) treated patients. During the eight week double-blind treatment period, incidence rates for all adverse experiences and for drug-related adverse experiences were similar between the two treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neurocognitive effects of aluminum.

The neurocognitive effects of aluminum (Al) were studied in 35 hemodialysis patients. Higher Al levels were associated with a decline in visual memory. As Al levels increased, patients with lower vocabulary scores (a measure of premorbid intelligence) showed a decline in attention/concentration, frontal lobe functions, and on several neurocognitive measures, while those with higher vocabulary scores revealed no Al-related decline. These results suggest that individuals with lower verbal intelligence may possess less well-developed compensatory strategies to overcome the neurocognitive effects associated with Al. These data also indicate that Al is neurotoxic and, therefore, potential sources of environmental Al should be identified and eliminated.

Adult↗

EEG spectra in dyslexic and normal readers during oral and silent reading.

EEGs of extensively screened dyslexics and normal readers were recorded while they read easy and difficult texts silently and orally, and during two other verbal tasks which also differed in overt speaking but had no reading component: narrative speaking and listening to a story. Mid-temporal, central and parietal leads were referenced to linked ears and to Cz. Large differences between tasks and between groups were found. With the linked ears reference, power was higher in all bands in oral reading than in silent reading, with the largest change occurring in the temporal leads. In the theta and low beta bands the difference between oral and silent reading was greater for controls than for dyslexics. These effects were not accounted for by differences in reading speed or in difficulty. Similar results were found in two cohorts of subjects. The difference between groups in theta was found only in the reading tasks. In contrast, the group difference in low beta was also found in the change from listening to speaking. This implies that the oral-silent group difference in theta is related to some aspect of the reading tasks other than the presence or absence of overt speaking, and that the low beta group difference is related to some aspect of overt speaking rather than to reading per se. With the Cz reference no group differences were found. It is suggested that the groups differ in the reading strategies they use, and the degree to which they shift strategy between the silent and oral tasks. We hypothesize that these cognitive differences are reflected in the theta activity from the temporal lobe. While there were many differences between the tasks in alpha power and asymmetry, no group differences involving alpha were found.

Adolescent↗

Antihypertensive effect of dilevalol is directly related to dose and plasma concentrations.

Dilevalol is a novel antihypertensive agent combining vasodilation due to selective beta 2-adrenergic receptor agonism with nonspecific beta antagonism. To determine the relation of dilevalol dose and plasma concentration to antihypertensive effect, dilevalol (n = 15) or placebo (n = 3) was administered to 18 hypertensive subjects. The study was performed under blinded conditions during a 21-day hospitalization after a 3-week drug-free outpatient phase. In the 15 hypertensive patients receiving dilevalol orally in single morning doses of 200, 400 and 800 mg each for 5 days, the drug was shown to reduce blood pressure effectively for 24 hours at all doses. The antihypertensive effect was significantly related to dose administered and to the concentration of unchanged dilevalol measured in plasma. Dilevalol did not cause excessive changes in heart rate at rest and did not produce postural hypotension. The antihypertensive effectiveness of dilevalol was essentially the same after the first and fifth (steady state) doses at each dose level. Finally, no tendency toward rebound hypertension or tachycardia was observed after the abrupt discontinuation of dilevalol in these patients.

Adult↗

EEG alpha asymmetry in dyslexics during speaking and block design tasks.

Lateral specialization for speech and spatial construction was investigated in a highly screened group of dyslexic and normal-reading boys, age 9-13, by examining the extent to which their EEG alpha asymmetry changed from one task to the other. EEG was recorded from central, midtemporal, and parietal leads during several minutes of spontaneous narrative speech, and while the child constructed block designs. The dyslexics showed the same strongly task-dependent asymmetry as the normal readers, comparable to that observed in our adult populations. The observations were confirmed with a second independently chosen cohort of subjects. This result is discussed in terms of the constraints it places on models of dyslexia which invoke disorders of lateral specialization and hemisphere integration.

Adolescent↗

On-line sensors for coagulation proteins: concept and progress report.

The assessment of blood damage and of the activation of the coagulation, complement and/or inflammatory systems by cardiovascular and extracorporeal devices is difficult at best. Immunoassay methods are now available for the measurement of many of the proteins, enzymes and peptides involved in coagulation, thrombosis, complement and inflammation. We present a long-range project and plan to develop an array of remote, on-line, semicontinuous immunosensors for selected coagulation proteins, based on fluoroimmunoassay principles. The free/bound separation step is performed optically. Excitation of fluorescence is performed via an evanescent wave produced by total internal reflection and waveguide optics. Fluorescence emission is collected only in the near field. Means to deliver fluorescently-labelled reagent and to modify the antigen-antibody binding constant are presented and discussed. The results of non-specific binding, plasma-blood fluorescence, and blood compatibility are also discussed.

Biocompatible Materials↗

EEG spectra in dyslexic and control boys during resting conditions.

We studied the resting eyes open and eyes closed EEG in carefully screened samples of 9-13-year-old dyslexic and control boys within a 2-cohort cross-validation design with repeat testing 1-3 years later. We found: no difference between groups in delta or theta activity in either cohort or in repeat testing 1-3 years later; in the dyslexics, decreased beta (19-24 c/sec) activity at bilateral central, parietal and mid-temporal leads referenced to vertex; inconsistent group differences in the alpha band: the first cohort dyslexics had lower alpha power than did the controls, but there was no group difference in the second cohort; and significant relative delta differences between groups in the first cohort, which were shown to be a statistical artifact of the use of relative power. We conclude that: dyslexia per se is not associated with increased absolute power in the delta and theta bands; lower power in the high beta band is reliably found in these samples of dyslexics without other disorders; and alpha power levels are not consistently lower in the dyslexic group.

Alpha Rhythm↗