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Biomedical subjects

R H Jackson

Publications and source records attributed to R H Jackson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Comparison of antagonist and agonist binding to the leukotriene B4 receptor intact human polymorphonuclear neutrophils (PMN).

In the present studies, the pharmacology of the leukotriene B4 (LTB4) receptor on intact human polymorphonuclear neutrophils (PMN) was characterized using radioligand binding techniques with [3H]LTB4 and a novel LTB4 receptor antagonist radioligand [3H]CGS 23131 (LY223982). Saturation studies revealed that [3H]CGS 23131 labeled a single class of recognition sites with high affinity (Kd = 13 nM) and limited capacity (apparent Bmax = 2.8 pmol/10(7) cells). In contrast, [3H]LTB4 labeled both a set of high (Kd = 0.3 nM) and lower affinity (Kd = 5 nM) recognition sites. However, the apparent density of [3H]LTB4 binding to intact human PMN (combined Bmax = 380 fmol/10(7) cells) was approximately 14% of that observed with [3H]CGS 23131. In ligand competition studies, various LTB4 agonists and antagonists were found to inhibit the binding of [3H]CGS 23131, revealing a pharmacological profile consistent with the specific labeling of the LTB4 receptor. A positive rank order correlation (r = 0.79) was observed between the ligand competition profiles obtained with [3H]CGS 23131 and [3H]LTB4. Both LTB4 and its omega oxidation product, 20-OH-LTB4, were found to inhibit the binding of 1.0 nM [3H]CGS 23131 in a biphasic fashion consistent with the existence of multiple affinity components of the LTB4 receptor. In competing for 0.5 nM [3H]LTB4 binding, these compounds were found to produce monophasic inhibition curves, which was indicative of a selective interaction at the high-affinity LTB4 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzophenones↗
PubMed1992

Characterization of rat lung endothelin receptor subtypes which are coupled to phosphoinositide hydrolysis.

The ability of endothelin (ET) isopeptides to interact with ET receptor subtypes and stimulate phosphoinositide (PI) hydrolysis was examined in the rat lung. [125I]ET-1 and [125I]ET-3 binding to lung homogenates was saturable with maximal binding capacity values of 438 and 125 fmol/mg of protein and Kd values of 29 and 13 pM. The nonselective peptides, ET-1 and ET-2, produced steep inhibition of both [125I]ET-1 and [125I] ET-3 binding. The ETB-selective peptides, ET-3, sarafotoxin (SFX) S6a, SFX S6b and SFX S6c and the ETA-selective antagonist, BQ-123, generated shallow inhibition curves of [125I]ET-1 binding indicating the presence of both ETA and ETB receptors in the lung. Whereas the peptides exhibited similar potency in stimulating PI turnover in rat lung slices, the ability of ET-3 (1.6-fold) and SFX S6c (2-fold) to maximally stimulate [3H]inositol phosphate release was significantly different from the maximal response produced by ET-1 (4-fold) or SFX S6b (3.2-fold). The ETA-selective antagonist, BQ-123 [cyclo(L-Leu-D-Trp-D-Asp-L-Pro-D-Val)], inhibited PI hydrolysis induced by ET-1 or SFX S6b by approximately 80%, although having no effect on ET-3- or SFX S6c-induced PI turnover. Furthermore, ET-1- and SFX S6b-stimulated [3H]inositol phosphate release was significantly decreased in the presence of quinacrine and nordihydroguairetic acid, but not indomethacin. In contrast, these inhibitors had no effect on PI hydrolysis induced by SFX S6c.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Phage-enzymes: expression and affinity chromatography of functional alkaline phosphatase on the surface of bacteriophage.

We have demonstrated that an active enzyme can be expressed on the surface of a bacteriophage. The gene encoding alkaline phosphatase from Escherichia coli was cloned upstream of gene 3, which encodes a minor coat protein of the filamentous bacteriophage, fd. A fusion protein of the correct size was detected from viral particles by Western blotting. Ultrafiltration confirmed that the enzyme fusion behaves as part of a larger structure as would be expected of an enzyme fused to a viral particle. Both wild-type alkaline phosphatase (Arg166) and an active site mutant (Ala166) expressed in this way retain catalytic activity and have qualitatively similar kinetic properties to free enzyme. Values were obtained for Km of 72.7 and 1070 microM respectively whilst relative kcat for the mutant was 36% of that for wild-type. Phage particles expressing alkaline phosphatase were bound to an immobilized inhibitor (arsenate-Sepharose) and eluted with product (20 mM inorganic phosphate). In this way, the functional enzyme is co-purified with the DNA encoding it. This may permit a novel approach to enzyme engineering based on affinity chromatography of mutant enzymes expressed on the phage surface.

Alkaline Phosphatase↗
PubMed1991

Patient reading ability: an overlooked problem in health care.

Health care workers often assume that patients who have completed a certain grade in school can read at that level. This study examines the relationships between patient reading ability, the last grade completed, and the reading ability necessary to comprehend commonly used written materials. We tested 528 patients during regular visits to seven outpatient clinics serving a predominantly indigent population. In addition, we analyzed the readability of 280 brochures and consent forms used in these clinics. Most patients had reading abilities on a level far below their last grade completed, while almost all materials tested were written on a level far above average patient reading ability. We conclude that patient reading ability should be routinely tested and that written materials should be developed on a level commensurate with patient reading ability.

Adolescent↗
PubMed1991

Rapid assessment of literacy levels of adult primary care patients.

Health education materials, medical instructions, consent forms, and self-report questionnaires are often given to patients with little regard for their ability to read them. Reading ability is rarely tested in medical settings. The Rapid Estimate of Adult Literacy in Medicine (REALM) was developed as a quick screening tool to assist physicians in identifying patients with limited reading skills and in estimating patient reading levels. This information can be used to tailor materials and instructions to patients' abilities. The REALM and the reading sections of the Peabody Individual Achievement Test-Revised and the Slosson Oral Reading Test were used to test reading ability in 207 adults in six public and private primary care clinics. REALM scores correlated highly with those of the standardized reading tests. The REALM, which takes three to five minutes to administer and score, appears to be a practical instrument to estimate patient literacy in primary care, patient education, and medical research.

Adolescent↗
PubMed1990

Esophageal perforation due to nasogastric intubation.

Esophageal perforation is a rare but catastrophic complication of nasogastric intubation. Diagnosis is frequently delayed, resulting in high mortality. We report a case of perforation due to nasogastric intubation in an otherwise normal esophagus. Patients at high risk of this complication can be identified, and special techniques can be used to avoid perforation. Percutaneous endoscopic gastrostomy is an alternative to nasogastric intubation for long-term enteral feeding. When nasogastric intubation is performed, clinical tests of tube position are not sufficient to guarantee proper tube position. The tip of the tube must be visualized radiographically in the stomach prior to initiation of tube feeding. When perforation does occur, proper management is often controversial. Therapy must be tailored to each individual case for the best possible outcome.

Aged↗
PubMed1989

Autoradiographic characterization of high-affinity adenosine A2 receptors in the rat brain.

Binding of the non-selective adenosine receptor agonist, [3H]NECA (5'-N-ethylcarboxamidoadenosine) was evaluated in sections of rat brain using quantitative receptor autoradiography. [3H]NECA bound specifically to a variety of different brain regions including striatum, cerebellum and thalamus. In the presence of the selective adenosine A1 receptor agonist, cyclopentyladenosine (CPA: 50 nM), [3H]NECA binding was exclusively localized to the striatum and olfactory tubercle. Binding in rat striatum occurred at a single site (Kd = 9 nM) with limited capacity (apparent Bmax = 230 fmol/mg tissue). Competition experiments in both striatum and olfactory tubercle with various adenosine agonists and antagonists indicated that the sites labeled by [3H]NECA in the presence of 50 nM CPA were A2 in nature, the rank order of activity for agonists being NECA greater than 2-chloroadenosine (2-CADO), greater than R-N6-phenylisopropyladenosine (R-PIA) greater than CPA greater than S-N6-phenylisopropyladenosine (S-PIA). For xanthine antagonists the order was greater than 1,3-dipropyl-8(2-amino-4-chloro)phenylxanthine (PACPX) greater than xanthine amino acid congener (XAC) greater than xanthine carboxylic acid congener (XCC) greater than 1,3-diethyl-8-phenylxanthine (DPX). The localization of A2 receptors to discrete regions of rat brain indicates that the purine may have a selective role in modulating basal ganglia function.

Adenosine↗
PubMed1989

Synthesis, opioid receptor binding profile, and antinociceptive activity of 1-azaspiro[4.5]decan-10-yl amides.

A series of azaspiro[4.5]decanyl amides were prepared by a novel cyclization route and examined for opiate receptor binding and antinociceptive activity. Selected tertiary amides in this series showed potent selective mu-receptor binding and antinociceptive activity, in contrast to the less conformationally restricted secondary amides, which showed relatively weak activity. Although structurally similar to the kappa-agonist U-50488H (1), these compounds showed virtually no tendency to bind to the kappa-receptor. An X-ray crystal structure of compound (21) confirms that the spirocyclic amine does not cause distortion away from the chair conformation of the cyclohexane ring. Either this receptor has very specific requirements for the orientation of the two nitrogens of these compounds or this ring system fills a portion of space more readily tolerated by the mu- and delta-receptors.

Analgesia↗
PubMed1989

4-(Phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids: synthesis, activity at N-methyl-D-aspartic acid receptors, and anticonvulsant activity.

A series of 4-(phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids were synthesized, and their biological activity was assessed as competitive ligands for the NMDA receptor, both in vitro by using a receptor binding assay ([3H]CGS 19755 binding) and in vivo by using an NMDA seizure model in mice. The analogues were also evaluated in [3H]AMPA and [3H]kainate binding to assess their affinity for non-NMDA excitatory amino acid receptor subtypes. A number of these analogues show potent and selective NMDA antagonistic activity both in vitro and in vivo. Most notable are 4-(phosphonomethyl)-2-piperidinecarboxylic acid (1a) (CGS 19755) and the phosphonopropenyl analogue 1i, both of which show anticonvulsant activity in the 1-2 mg/kg ip range. With the aid of computer-assisted modeling, a putative bioactive conformation for AP-5 is hypothesized from the SAR data presented and a preliminary model for the antagonist-preferring state of the NMDA receptor is presented.

Animals↗
PubMed1989

Benzofuro[2,3-c]pyridin-6-ols: synthesis, affinity for opioid-receptor subtypes, and antinociceptive activity.

A general synthetic approach to a novel series of cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols is described together with their receptor-binding profile on opioid-receptor subtypes (mu, kappa, delta). In addition, their in vivo antinociceptive activity was assessed. A number of the analogues synthesized showed potent affinity for opioid receptors and have potent antinociceptive activity in a mouse phenylquinone abdominal stretching model. In addition, the SAR for nitrogen substitution in the above series is explored with respect to the overall opioid receptor subtype binding profile. In general it was found that substituents which enhanced mu and kappa binding affinity in the benzomorphan series had a similar effect in the benzofuropyridine series described in this manuscript. An overlap hypothesis topologically connecting the benzomorphan nucleus to the cis-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridine nucleus is also presented.

Analgesics↗
PubMed1988

Anatomical distribution of vasoactive intestinal peptide binding sites in peripheral tissues investigated by in vitro autoradiography.

Vasoactive intestinal polypeptide has a widespread distribution in the body, occurring in both the central and peripheral nervous systems and considerable information is available on its distribution, physiology, and pharmacological actions. Receptors for VIP have been demonstrated previously in peripheral tissues by conventional binding techniques using isolated membrane preparations. However, information on their precise localization is limited. We therefore localized binding sites in a variety of guinea pig and rat tissues by in vitro autoradiography and made a parallel study of the distribution of VIP nerves in these tissues using immunocytochemistry. [125I]VIP was prepared by the chloramine T method and shown to be pharmacologically active. After a preincubation procedure to remove endogenously bound VIP, unfixed cryostat sections were incubated with 1 nM [125I]VIP. To determine specific binding, sections were incubated in the presence or absence of 1 microM unlabeled VIP. Autoradiograms were generated by exposing the sections to LKB-Ultrofilm or emulsion-coated coverslips. Dense binding occurred in discrete locations within the gastrointestinal, respiratory, and genital tracts, correlating with known actions of VIP and, to various extents, with the distribution of VIP nerves. For example, there was precise localization to respiratory epithelium, smooth muscle of airways and blood vessels, and alveolar walls, in keeping with the effects of VIP on vascular and airway smooth muscle and mucus secretion.

Animals↗
PubMed1988

The work of the Child Accident Prevention Trust.

In 1983 an article was published in this Journal describing the work of the Child Accident Prevention Trust. Since that time many developments have taken place in the field of child accident prevention. There has been an increased recognition of the role of accidents and injuries in child health and the importance of accident prevention at an international, national, and local level. This has, in part, been a result of work undertaken by the Child Accident Prevention Trust. Much remains to be done, however, and doctors and other health workers involved with children must recognise the part that they can play in reducing this epidemic. Mortality and morbidity from accidents is the largest single problem in the health of children after the first year of life. The aim of this article is to stimulate interest in the problem of accidents in childhood especially among community paediatricians and clinical medical officers. Hospital doctors and general practitioners also have a particular part to play in drawing the attention of appropriate authorities to factors which have led to accidents that may have been preventable (see Annotation in this issue).

Accident Prevention↗
PubMed1987

Distribution of vasoactive intestinal polypeptide binding sites in guinea pig genital tissues.

Vasoactive intestinal polypeptide (VIP) binding sites were localised in sections of guinea pig genital tissues using [125I]VIP and quantitative in vitro receptor autoradiography. A moderate density of binding was demonstrated in the epithelium of the prostate gland, seminal vesicles and in the testes. Moderate to high VIP binding also occurred in the epithelial lining of the oviduct, uterine glands, cervix and vagina. The binding sites appear to have a dissociation constant (Kd) of 0.36 nM and maximum receptor density (Bmax) of 60.5 x 10(-3) fmol/mm2 in sections of the uterine horn. The results indicate that VIP may have a role in the secretory functions of the guinea pig genital tract.

Animals↗
PubMed1987

Duodenal ulceration: review of 110 cases.

This paper describes 110 cases of childhood duodenal ulcer, which were diagnosed over 26 years: 63 were diagnosed by barium meal examination; 47 by upper gastrointestinal endoscopy. The mean age at diagnosis was 11.2 years, with symptoms reported in 46% before 10 years and in 15% before 6 years of age. There was often a considerable delay in diagnosis, particularly in the younger age group. Nocturnal pain (61%) and a close family history of duodenal ulcer disease (62%) were the most valuable pointers to the diagnosis. Fifteen children had required surgery for persistent symptoms. Thirty four had received treatment with an H2 receptor antagonist, and all but four had had a satisfactory initial response. Seventy per cent relapsed within six months of discontinuing treatment, and long term maintenance treatment may therefore be necessary.

Adolescent↗