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J Dickson

Publications and source records attributed to J Dickson.

At least 19 recordsLinked to original sources
PubMed1997

Evaluation of a low-threshold clinic for opiate-dependent drug users.

This study reports on the development and outcome of a Low Threshold Clinic (LTC) for opiate-dependent drug users. The service originated as a nursing initiative within an inner city Drug Dependency Centre (DDC) and its rationale and treatment approach are explored in relation to the literature and local circumstances. Client baseline and outcome data were systematically gathered to assess service uptake and service efficacy in terms of client outcome. Data are presented for the first two years of operation during which a total of 59 clients entered the LTC. The sociodemographic characteristics and patterns of drug use among this group suggest the service was successful in targeting clients who previously failed to enter traditional treatment programmes despite initial referral to the DDC. Outcome data indicate a tendency for clients to inject less frequently, engage in less criminal activity and, by 12 months, to reduce their dose of prescribed methadone whilst attending the LTC. Tentative conclusions are drawn concerning the value of this service for 'hard-to-reach' drug users and those who may be at a precontemplation stage of change. Recommendations are made for a more comprehensive evaluative study that involves comparison with other treatment approaches.

Adult↗
PubMed1996

Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.

The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was sequenced. A novel G to T transversion at codon 202, predictive of an exchange of tryptophan 202 by cysteine, was identified. As the mutation occurs at G-1 of the 5' splice donor site of intron 3, aberrant splicing is also likely. The mutation involves one of the supposed water pore-forming loops. Therefore, both aberrant splicing and amino acid substitution are likely to result in a functionally defective protein. Sequencing of the complete V2R gene of the male patient of family 2 revealed a novel single-base deletion at codon 310 (delta C1001), shifting the reading frame to give an altered amino acid sequence beginning at codon 311. The mutation is unique in predicting a C-terminally extended protein (termination after codon 434 in the mutant receptor instead of codon 371 in the wild-type). The deduced mutant protein is likely to be nonfunctional since the amino acid sequence of the seventh transmembrane domain and the C-terminus is altered.

Amino Acid Sequence↗
PubMed1996

Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function.

We investigated the biochemical and functional properties of five vasopressin V2 receptor mutants (L44F, L44P, W164S, S167L, and S167T) that were recently described in families with a history of X-linked nephrogenic diabetes insipidus. COS.M6 cells transfected with cDNA encoding these mutants acquired < 4% specific [3H]arginine vasopressin (AVP) binding sites on the cell surface in comparison with cells transfected with cDNA coding for the wild-type receptor. Membrane preparations from COS.M6 cells or human embryonic kidney 293 cells expressing these mutants did not respond with an increase in adenylyl cyclase activity in response to AVP, which is in contrast to membranes from cells expressing the wild-type. By analyzing fusion proteins of the V2 receptor and Escherichia coli alkaline phosphatase attached to the carboxyl terminus of the receptor moiety, we found that the mutants L44P, W164S, S167L, and S167T lacked complex glycosylation and were expressed at low levels. The data suggest that the mutants L44P, W164S, S167T, and S167L are misfolded and therefore retained within the endoplasmic reticulum and degraded. In contrast, the fusion proteins carrying the mutant L44F and the in vitro mutant S167A were expressed in their mature form at wild-type levels; however, only the mutant S167A was functionally active. Site-directed mutagenesis of S167 revealed that elimination of the endogenous hydroxyl group (S167A) yielded a protein with properties identical to those of the wild-type receptor, whereas both the introduction of a methyl group (S167T) and the replacement of the hydroxyl group by an isopropyl group (S167L) profoundly disturbed receptor processing. The data show that minute changes at codon 167 nearly abolish expression of a mature protein, thus defining structural requirements of this codon.

Alkaline Phosphatase↗
PubMed1995

Second messenger systems in Tourette's syndrome.

Abnormalities within second messenger systems have been hypothesized as the underlying pathophysiologic mechanism in a variety of neuropsychiatric disorders. In the Gilles de la Tourette syndrome (TS) prior studies have shown that the concentration of adenosine 3',5'-monophosphate (cAMP) is reduced in cortical and putamen brain regions. In this study, postmortem cortical tissues from 4 adults (mean age 59.5 years) with the lifetime diagnosis of TS and 5 controls (mean age 63.8 years) were analyzed for functional activities within the cAMP and phosphoinositide systems. In addition, plasma cAMP was quantified in children with TS (n = 33) and controls (n = 17). In frontal (A4, A6) and occipital (A17) cortical tissues there were no significant differences for adenylyl cyclase activity whether assayed under basal conditions or after stimulation with GTP gamma S (a non-hydrolyzable GTP analog), forskolin (a selective enzyme stimulator), or (-)-isoproterenol (a beta-adrenergic agonist). D2 receptor activation (quinpirole) and assessment of the inhibitory guanine nucleotide protein also showed no significant alterations in TS samples. Activity of cAMP phosphodiesterase was increased insignificantly in A4 and A17 TS brain regions. Plasma concentrations of cAMP in plasma were similar in children with TS (135.4 +/- 8.3 pmol/ml) and controls (132.6 +/- 7.9 pmol/ml). Postmortem membrane receptor binding for markers within the phosphoinositide (PI) system showed that TS samples had increased [3H]phorbol ester binding to protein kinase C sites in area A17, but normal binding in A4. In contrast, [3H] inositol 1,4,5-triphosphate binding to IP3 receptors showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1994

Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus.

Families with congenital nephrogenic diabetes insipidus were analyzed with regard to mutations in the vasopressin V2 receptor gene. Family 1 shows an X-chromosomal recessive inheritance of the disease over 4 generations. A patient from this family was found to have a T-->A transversion at nucleotide 1095, predictive for a substitution of serine 167 (which is highly conserved among G-protein-coupled receptors), by threonine. Both the mutant and the normal allele were detected in the maternal genome. The patient's healthy brother was homozygous for the normal allele. The patient from family 2 showed a T-->C transition at nucleotide 727, predictive for a substitution of leucine 44 by proline. Analysis of the maternal genome revealed homozygosity for the normal allele. Thus a de novo mutation seems to have occurred. The nature and site of the mutation in family 2 suggest that it is responsible for the patient's disease.

Amino Acid Sequence↗
PubMed1994

Speed of onset of sensory block for elective extradural caesarean section: choice of agent and temperature of injectate.

We have studied the effects of choice of local anaesthetic and temperature of extradural injectate on speed of onset of sensory block for elective extradural Caesarean section in a double-blind trial in 120 women allocated randomly to one of four groups to receive either plain 0.5% bupivacaine or 2% lignocaine with 1:200,000 adrenaline at either room temperature or 38 degrees C. The onset time of lignocaine with adrenaline was shorter than that of bupivacaine regardless of temperature (P < 0.01). Warmed lignocaine produced the most rapid block overall (P < 0.025). The incidence of hypotension, ephedrine requirement, shivering, quality of analgesia and additional analgesic requirements were similar for all groups.

Anesthesia, Epidural↗
PubMed1993

Antigenic diversity of a major merozoite surface molecule in Theileria annulata.

The 30-kDa merozoite surface antigen of Theileria annulata (Ankara) has been characterised by using merozoites derived from differentiating macroschizont-infected cloned cell lines. This molecule was found to be 1 of the major polypeptides in extracts of both merozoites and piroplasms and was strongly detected by serum from an immune cow. Analysis of merozoite extracts derived from cloned cell lines infected with parasites of different genotypes detected 2 forms of this molecule, with respective molecular masses of 30 kDa and 32 kDa. These 2 molecules were shown to be related to each other by peptide mapping. In addition to the observed size differences, the molecules were found to be antigenically divergent. Periodate treatment of western blots demonstrated that at least 1 of the variable antigenic determinants was generated by secondary modification of the polypeptide and that a large amount of the antibody reactivity was directed against similar moieties. Parasite stocks isolated from different geographical regions were distinguished by analysis of the molecules within the 30-32-kDa molecular region. The relationship between T. annulata molecules and similar antigens described for other Theileria species is discussed.

Animals↗
PubMed1993

Costs of on-call.

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Costs and Cost Analysis↗