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D Jones

Publications and source records attributed to D Jones.

At least 883 records · Page 49Linked to original sources

Post-translationally modified 14-3-3 isoforms and inhibition of protein kinase C.

This report compares the ability of individual members of the 14-3-3 protein family to inhibit particular protein kinase C (PKC) isoforms. We also show that two of these 14-3-3 isoforms (alpha and delta) specific to mammalian and avian brain are in vivo post-translationally modified forms of beta and zeta respectively. The presence of this modification enhances the activity of 14-3-3 as an inhibitor of protein kinase C nearly two fold. A method for analysing isoforms of 14-3-3 on acid-urea gels is also described. This permits the complete separation of all major isoforms and their unequivocal identification by a range of isoform specific antisera. The activity of recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse phase HPLC are compared. The effects of diacylglycerol and the phorbol ester, PMA (phorbol 1 2-myristate 13 acetate) on the inhibition suggest that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC.

14-3-3 Proteins↗

Psychoactive substance use disorder in relatives of patients with anorexia nervosa.

We assessed the lifetime prevalence and morbid risk of psychoactive substance use disorder (SUD; alcoholism and drug use disorder) in the first- and second-degree relatives, excluding children, of 34 female patients with anorexia nervosa (AN) and 34 age- and sex-matched controls who had no history of an eating disorder. Diagnoses of relatives were made blind to probands' diagnoses. The prevalence of SUD was 9% in both anorectic and control relatives, and the figures for morbid risk were 14% and 15%, respectively; these differences were nonsignificant. These results suggest that adolescent and adult women with AN do not possess many of the familial factors that predispose to the development of psychoactive SUD.

Adolescent↗

The appearance of endogenous opiates in cerebrospinal fluid following opiate injection in various animal species.

Phenylquinone writhing, tail-flick, stimulated guinea pig ileum and mouse vas deferens were used to quantitate opiate-like activity in CSF taken prior to and at various times after the injection of morphine. The injection of various doses of morphine caused a dose responsive increase in opiate-like material in rabbit CSF taken at the peak of activity (60 min later). Morphine also caused an increase in opiate activity in dog CSF. Quantitation of radioactivity in CSF after the injection of radiolabelled morphine, stability studies and other assays were used to rule out the possibility that the increased activity in CSF was due to morphine itself. CSF taken after morphine injection produced a peak on HPLC with a 15 minute retention time which was not present in CSF taken prior to the injection. This peak was not caused by morphine, met-enkephalin, leu-enkephalin, dynorphin 1-13 or beta-endorphin which have retention times of 5, 7, 9, 22 and 30 minutes, respectively. Preinjection of the rabbit with naloxone blocked the increased opiate-like effects of CSF taken after morphine and the opiate effects of the CSF were antagonized by naloxone injected into mice or the isolated organ bath.

Animals↗

Lectin histochemistry of cerebral microvessels in ageing, Alzheimer's disease and Down's syndrome.

A panel of 14 lectins was used to investigate the expression of saccharides by cerebral microvessels (MBV) in ageing, Alzheimer's disease (AD) and Down's syndrome (DS). Broad increases in lectin binding with age may reflect changes in amount and diversity of glycoproteins due to the thickening of the basement membrane (BM) common in older persons. In AD, and in persons over 50 years of age with DS, binding of e-PHA, 1-PHA and PAA was increased beyond that of age alone, as was that of UEA-I and BSA-1B4 in AD, but not in DS. Persons under 50 years of age with DS showed no changes inappropriate to their age. These specific increases in AD and DS may reflect selective disease-related changes in BM and could indicate an impaired blood-brain barrier (bbb) function or integrity. However, because they occur (in DS) after the deposition of amyloid (A4) protein and onset of neurofibrillary degeneration, it is unlikely they induce plaque and tangle formation. Such changes in MBV could stem from the loss of neurones from locus caeruleus, raphe and nucleus basalis (which are thought to innervate MBV and exert control over blood flow and permeability) that occurs in DS after 50 years of age.

Adolescent↗

Toxins produced by arthropod parasites: salivary gland proteins of human body lice and venom proteins of chelonine wasps.

A review is presented of our ongoing research projects on the protein components of the saliva of human body lice and of the non-paralyzing venom of wasps in the subfamily Cheloninae. Sodium dodecyl sulfate-polyacryamide gel electrophoretic analysis of lice salivary gland proteins showed a predominance of high and intermediate mol. wt proteins. Immunoblotting with a low titer polyclonal antiserum to lice salivary proteins indicated that some, but not all, of the predominant high mol. wt salivary gland proteins are injected into the host during feeding. The venom of a Chelonus sp. wasp contains a chitinase, and a 33,000 mol. wt protein with a primary structure composed mostly of a series of 12 tandem repeats of a 14-residue sequence. The N-terminus of this protein and its homologs in a related species of Ascogaster share a conserved adjacent pair of acidic residues. Epitope mapping/immunoprecipitation experiments now in progress will provide information on which linear motifs are on the surface of the protein, and will thereby provide information on the tertiary structure of the protein.

Animals↗

Posture-related tachycardia in older patients with hyponatremia.

Hyponatremia (HN) is the commonest electrolyte abnormality in elderly patients. Its etiology in this setting is poorly understood. In this study, the authors aim to compare the hemodynamic and hormonal responses of a group of older patients with a predisposition to HN with a group of age-matched controls. We assessed hemodynamic and hormonal responses to postural challenge in 15 patients over age 65 with serum sodium concentrations of less than 130 mM (mean 128.7 mM) and 15 age-matched controls with normal sodium concentrations. Patients remained recumbent for 1 h and stood for the second. Blood was drawn at baseline and at 15 min intervals. Blood pressure (BP) and pulse rates (PR) were monitored electronically. Plasma arginine vasopressin (AVP), atrial natriuretic peptide (ANP), renin and aldosterone were determined periodically during the study period. No difference in BP between groups was noted. PR increased significantly in the HN group only within 3 min of standing (from 71 +/- 4 to 86 +/- 5, P<0.01) and remained significantly higher than controls until 90 min (87 +/- 5 vs. 69 +/- 4, P<0.01). While plasma AVP levels increased significantly following 30 min standing and remained elevated for both HN and control groups, it did not differ significantly between the two. Baseline plasma ANP levels were significantly higher in HN patients compared with controls and remained significantly higher (P<0.05) throughout the study. There was no significant difference in plasma renin or aldosterone levels between groups during the study period. We have demonstrated differing autonomic and hormonal responses to orthostatic challenge between HN patients and age-matched controls. Water retention due to the syndrome of inappropriate anti-diuretic hormone secretion (with reset osmostat) may lead to raised ANP levels in this older cohort of patients. Further physiological studies are required to clarify the precise mechanism of these varying responses.

Journal Article↗

Use of pharmacists by older people in the community.

A random sample of community dwelling elderly people (> 65 years) was interviewed on two occasions, 6 months apart. Four hundred and thirty five completed both interviews. Subjects were asked about their medication, and about the advice sought from community pharmacists, on both drug and non-drug related health issues. Medication had been altered during the 6-month interval in 101 (23%) of people, but only 15 of these had discussed the change with a pharmacist. The majority of those who did discuss their medication, however, found the exchange helpful. Only 1% of the sample had discussed a health problem not related to drugs with a pharmacist in the previous month, although once again such discussions were felt to be useful. Of the total sample, 79% said they would never discuss medication-related issues with a community pharmacist, and 83% would not discuss other health matters. The majority of this sample - 96% - expressed a preference to discuss these issues with their general practitioner.

Journal Article↗

Relationships between prescription and non-prescription drug use in an elderly population.

This paper explores, at an epidemiological level, the relationship between categories of over-the-counter (OTC) and prescribed (Rx) drugs in a community-resident elderly population. A total of 2818, randomly selected, older adults were interviewed at home about their use of prescribed and non-prescribed medication and other health-related factors. For comparative purposes OTC drugs were classified into 16 therapeutic groups-identical to those used by other researchers; prescribed drugs were classified into 45 British National Formulary (BNF) therapeutic sub-categories. Analyses revealed significant association between certain BNF categories and OTC categories, which may have a clinical explanation. These include a 3-fold increase (P<0.01) of OTC laxative use by those prescribed an antidepressant, and a 4-fold increase (P<0.001) in OTC antacid use among those prescribed oral corticosteroids. Our findings may indicate an attempt by older people to control side effects of prescription medicines with OTC preparations. This study, in part, supports the call by the Royal College of Physicians for further research to determine the effect of interactions (be they pharmacological, behavioural or otherwise) between OTC and prescribed medicines.

Journal Article↗

Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain.

Acute low back pain is a common problem in the emergency department (ED). Effective management of acute pain enhances early rehabilitation and recovery. Given the importance of inflammatory mediators in pain generation and the adverse effects associated with opioids, it is logical to expect that a non-opioid agent with antiinflammatory and analgesic properties would provide excellent analgesia with fewer adverse effects. This double-blind, randomized, multicenter clinical trial, performed in six university and community hospital EDs, compares the analgesic efficacy and adverse effects of ketorolac to those of acetaminophen-codeine in ED patients with acute musculoskeletal low back pain. Our hypothesis was that ketorolac would provide superior analgesia with fewer adverse effects. One hundred twenty-three patients with acute low back pain were randomized to receive ketorolac (KET, N = 63) or acetaminophen-codeine (ACOD, N = 60). Most (79%) were males, and the mean age was 34.5 years. After baseline clinical assessment, patients were treated with ketorolac (10 mg every 4 to 6 h as needed, up to four daily doses) or acetaminophen-codeine (600 mg-60 mg, respectively, every 4 to 6 h as needed, up to six daily doses) and followed for one week. Pain intensity was assessed on visual analogue and categorical scales. Functional capacity, overall pain relief, and overall medication rating were assessed on categorical scales. Adverse events were documented. Primary outcomes included: 1) Pain intensity differences, based on visual analogue scores, for the 0 to 6 h treatment phase. 2) Incidence of adverse events. Secondary outcomes included analgesic efficacy, functional capacity, and overall subjective drug evaluation at one week. Both drugs provided substantial pain relief, with maximal effect 2.2 h after oral dosing. There were no significant differences in analgesic efficacy, functional capacity, or overall pain relief between the two groups. Sixteen patients (10 KET vs. 6 ACOD, NS) withdrew prematurely because of drug inefficacy. Patients in the ACOD group reported significantly more adverse drug events and serious adverse drug events. Seven patients--all in the ACOD group--withdrew from the study because of adverse drug events. Based on comparable efficacy and a superior adverse event profile, ketorolac was preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED.

Acetaminophen↗

An innovative model of community collaboration in pediatric nursing.

Collaboration among nurses can lead to improved education and clinical practice and increased opportunities for nursing research. Although numerous descriptions of interinstitutional collaboration among nurses can be found, many projects are limited in scope or purpose. A more comprehensive approach can facilitate excellence in practice, education, and research throughout the community. By pooling professional resources, nurses across organizational lines can achieve common goals and reduce costs associated with services and programs. The purpose of this article is to describe an interinstitutional nursing model that supports collaboration while promoting standards of excellence.

Community Health Nursing↗

Considerations on the structural evidence of a ligand-binding function of ultraspiracle, an insect homolog of vertebrate RXR.

This analysis considers the structural evidence of a ligand-binding function of the nuclear receptor ultraspiracle (USP). The positions and nature of residues in the ligand-binding domain of USP from six higher insects is evaluated in comparison to the function of conserved residues vertebrate receptors that have been co-crystallized with ligand. USP appears to conserve residues that in vertebrate receptors (1) form the hydrophobic ligand-binding pocket, (2) contact oxygen-containing moieties on ligands, such as hydroxyl, keto and carboxyl groups, and (3) in response to ligand-binding conformationally change to form a multi-helix hydrophobic groove for recruitment of transcriptional co-activators. These structural features are consistent with the recent report that USP can bind the epoxymethylfarnesoates (juvenile hormones) and thereupon is induced to change conformation.

Amino Acid Sequence↗

Hair cells without supporting cells: further studies in the ear of the zebrafish mind bomb mutant.

Each sensory hair cell in the ear is normally surrounded by supporting cells, which separate it from the next hair cell. In the mind bomb mutant, as a result of a failure of lateral inhibition, cells that would normally become supporting cells differentiate as hair cells instead, creating sensory patches that consist of hair cells only. This provides a unique opportunity to pinpoint the functions for which supporting cells are required in normal hair cell development. We find that hair cells in the mutant develop an essentially normal cytoskeleton, with a correctly structured hair bundle and well-defined planar polarity, and form apical junctional complexes with one another in standard epithelial fashion. They fail, however, to form a basal lamina or to adhere properly to the adjacent non-sensory epithelial cells, which overgrow them. The hair cells are eventually expelled from the ear epithelium into the underlying mesenchyme, losing their hair bundles in the process. It is not clear whether they undergo apoptosis: many cells staining strongly with the TUNEL procedure are seen but do not appear apoptotic by other criteria. Supporting cells, therefore, are needed to hold hair cells in the otic epithelium and, perhaps, to keep them alive, but are not needed for the construction of normal hair bundles or to give the hair bundles a predictable polarity. Moreover, supporting cells are not absolutely required as a source of materials for otoliths, which, though small and deformed, still develop in their absence.

Animals↗

A school-based strategy to assess children's environmental exposures and related health effects in economically disadvantaged urban neighborhoods.

The School Health Initiative: Environment, Learning, Disease (SHIELD) study is a novel school-based investigation of children's environmental health in economically disadvantaged urban neighborhoods of Minneapolis. This article describes the study design and summarizes lessons learned about recruiting and monitoring this historically understudied population. The SHIELD study focused on measuring children's exposures to multiple environmental stressors [volatile organic chemicals (VOCs), environmental tobacco smoke, allergens, bioaerosols, metals, pesticides, polychlorinated biphenyls (PCB), phthalates] and exploring related effects on respiratory health (e.g., lung function) and learning outcomes (e.g., standardized test scores, academic achievement). It involved intensive exposure monitoring, including environmental measurements inside and outside the children's schools and inside their homes, personal measurements with passive dosimeters worn by the children, and biological marker measurements in blood and urine. The SHIELD participants comprised a stratified random sample of 153 "index" children and 51 of their siblings enrolled in grades 2-5 at two adjacent elementary schools. The Minneapolis Public Schools (MPS) assisted with identifying, contacting, recruiting, and monitoring this population, which traditionally is difficult to study because families/children are highly mobile, speak a diversity of languages, frequently do not have a telephone, endure economic hardships, often do not trust researchers, and have a spectrum of unconventional lifestyles and living arrangements. Using a school-based approach, the overall SHIELD enrollment (response) rate was 56.7%, with a wide disparity between English-speaking (41.7%) and non-English-speaking (71.0%) families/children. Most children remained involved in the study through both monitoring sessions and exhibited an acceptable degree of compliance with study protocols, including providing blood and urine samples. Results indicate that it is both practical and affordable to conduct probability-based exposure studies in this population, but that it is also important to improve our understanding of factors (e.g., cultural, economic, psychological, social) affecting the willingness of families/children to participate in such studies, with special emphasis on developing cost-effective recruitment methods.

Air Pollution, Indoor↗

Prognostic value of markers of collagen remodeling in venous ulcers.

A 25 patient study was conducted into the relationship between markers of collagen metabolism in venous ulcer exudates and healing status, and their prognostic value in predicting healing performance. Wounds were sampled on at least 5 occasions over 12 months, the frequencies of which were determined by the need for clinic attendance. Specimens were taken from several sites on each ulcer using sterile preweighed filters. Wound margins were traced and sites recorded for each collection. Sample sites were evaluated for severity as improving, static, or deteriorating according to subsequent wound progression. Specimens were analyzed for levels of proenzyme and active forms of matrix metalloproteinases 2 and 9, neutrophil elastase, and type I collagen C propeptide. There was an overall trend of greater expression of all markers with increasing severity of wound site, this being highly significant for pro-matrix metalloproteinase-9 (p = 0.006). For samples collected simultaneously from improving and deteriorating regions of the same wound, paired data analysis showed statistically significant differences for pro-matrix metalloproteinase-9 (p < 0.001), neutrophil elastase (p < 0.005) and activated matrix metalloproteinase-9 (p < 0.05). Taken overall, these data show the potential of markers of collagen biochemistry as predictors of repair in venous ulcers; in particular pro-matrix metalloproteinase-9 and neutrophil elastase were found to be accurate prognostic indicators of subsequent healing.

Biomarkers↗

Persistent atypical lymphocytic hyperplasia following tick bite in a child: report of a case and review of the literature.

We report a 6-year-old girl who developed a red papule on the posterior neck at the site of a previous tick bite. Initial biopsy was performed a year after the bite and the specimen showed a dense lymphoid infiltrate with admixed CD30+ cells. The patient was referred to our center because of concern about the development of a CD30+ lymphoproliferative disorder. The lesion was completely excised. Histology showed no evidence of a clonal lymphoproliferative disorder or Borrelia infection, but persistence of CD30+ cells. This case demonstrates that a tick bite reaction can persist for more than 1 year and show immunophenotypic and morphologic overlap with a CD30+ lymphoproliferative disorder. Complete history with thorough clinical and histopathologic evaluation is necessary to arrive at the correct diagnosis.

Animals↗