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Biomedical subjects

E Johnstone

Publications and source records attributed to E Johnstone.

14 recordsLinked to original sources
PubMed2002

Bromocriptine use is associated with decreased smoking rates.

Dopaminergic transmission in the central nervous system is thought to underlie addictive behaviours, including smoking. One effective smoking cessation drug, bupropion, enhances dopaminergic transmission; conversely, antipsychotic drugs, which are dopamine antagonists, are associated with increased smoking. Thus we hypothesized that subfertile women treated with the potent dopamine agonist bromocriptine might smoke less as a consequence of their treatment. Among 4,608 subfertile women those conceiving on bromocriptine were half as likely to smoke as those taking other drugs or those conceiving without medication (p < 0.0001). This observation supports the role of dopamine in nicotine addiction, and suggests that bromocriptine-like drugs could be used effectively by pregnant women to aid cessation.

Bromocriptine↗
PubMed2001

Genetic clues to the molecular basis of tobacco addiction and progress towards personalized therapy.

The molecular processes that underlie addiction are beginning to unfold. Genetically determined variations in dopaminergic neurotransmission predispose to nicotine dependence. In addition, tobacco use is likely to be governed by the rate at which smokers metabolize nicotine. Functional polymorphisms in CYTOCHROME P450 monooxygenases that metabolize nicotine have now been defined and it should soon be possible to identify fast nicotine metabolizers by DNA analysis. Here, we review the key neurotransmitter receptors and metabolic enzymes implicated in tobacco dependence. We explore the potential benefits of classifying smokers according to the molecular aetiology of their habit. One major benefit will be in planning effective strategies for smoking cessation. Methods of typing for alleles related to smoking behavior that might be suitable for use in clinical practice in the future will also be discussed

Chromosomes↗
PubMed1999

Cytosolic phospholipase A2 is induced in reactive glia following different forms of neurodegeneration.

Many recent studies have emphasized the deleterious role of inflammation in CNS injury. Increases in free fatty acids, eicosanoids, and products of lipid peroxidation are known to occur in various conditions of acute and chronic CNS injury, including cerebral ischemia, traumatic brain injury, and Alzheimer's disease. Although an inflammatory response can be induced by many different means, phospholipases, such as cytosolic phospholipase A(2) (cPLA(2)), may play an important role in the production of inflammatory mediators and in the production of other potential second messengers. cPLA(2) hydrolyzes membrane phospholipids and its activity liberates free fatty acids leading directly to the production of eicosanoids. We investigated the cellular localization of cytosolic phospholipase A(2) in the CNS following: (1) focal and global cerebral ischemia, (2) facial nerve axotomy, (3) human cases of Alzheimer's disease, (4) transgenic mice overexpressing mutant superoxide dismutase, a mouse model of amyotrophic lateral sclerosis, and (5) transgenic mice overexpressing mutant amyloid precursor protein, which exhibits age-related amyloid deposition characteristic of Alzheimer's disease. We show that in every condition evaluated, cytosolic phospholipase A(2) is present in reactive glial cells within the precise region of neuron loss. In conditions where neurons did not degenerate or are protected from death, cytosolic phospholipase A(2) is not observed. Both astrocytes and microglial cells are immunoreactive for cytosolic phospholipase A(2) following injury, with astrocytes being the most consistent cell type expressing cytosolic phospholipase A(2). The presence of cytosolic phospholipase A(2) does not merely overlap with reactive astroglia, as reactive astrocytes were observed that did not exhibit cytosolic phospholipase A(2) immunoreactivity. In most conditions evaluated, inflammatory processes have been postulated to play a pivotal role and may even participate in neuronal cell death. These results suggest that cytosolic phospholipase A(2) may prove an attractive therapeutic target for neurodegeneration.

Alzheimer Disease↗
PubMed1999

Measuring the decline of a population of people with early-onset dementia in Lothian, Scotland.

OBJECTIVE: To seek differences in the pattern of decline between groups of patients with early-onset dementia of varying aetiologies (clinically defined) on the basis of the investigation of their different clinical profiles. DESIGN: A cohort of 126 live patients with dementia diagnosed before the age of 65, of various aetiologies, were identified using the Lothian Psychiatric Case Register. Each person was seen for two assessments approximately 1 year apart. SETTING: Patients were either in long-term care (NHS or other) or at home, usually in the care of relatives. PATIENTS: Of 126 cases (53 male, 73 female, mean age at referral 58 years), 114 met the diagnostic criteria for DSM-III-R dementia: 60 Alzheimer's type dementia; 13 multi-infarct dementia; 14 alcohol-related dementia; with 25 in a mixed group of overlapping categories and two in 'other' dementia types. By the second assessment, 18 cases had died and two cases refused reassessment. MEASURES: The data collected included: demographic; behavioural and psychopathological; neurocognitive; neurological; and genetic. Change was assessed. RESULTS: The alcohol group was distinguished from the other groups by its generally milder profile of impairment and a pattern of change indicating some areas of improvement in the follow-up period. CONCLUSIONS: There are limitations in the instruments used to measure change in this group of patients; at present, measures of change in dementing illnesses cater predominantly for an elderly population with Alzheimer's disease.

Adult↗
PubMed1999

People at risk of schizophrenia. Sample characteristics of the first 100 cases in the Edinburgh High-Risk Study.

BACKGROUND: The Edinburgh High-Risk Study is designed to explore the underlying pathogenesis of schizophrenia. AIMS: To establish the sample characteristics of the first 100 subjects in this study of young adults at risk of schizophrenia for genetic reasons, and to compare them with appropriate controls. METHOD: Details of the recruitment of the first 100 high-risk subjects aged 16-25 years into a prospective Scotland-wide study are given. Subjects and 30 age- and gender-matched normal controls were interviewed using the PSE, SADS-L and SIS and an unstructured psychiatric interview. RESULTS: Some significant differences emerged between the high-risk group and the control group, namely in previous psychiatric history (31 v. 6.3%), forensic contacts (19 v. 3.1%) and delinquent behaviour (20 v. 3.1%). There were also differences in some parameters from the SIS: childhood social isolation, interpersonal sensitivity, social isolation, suicidal ideation, restricted affect, oddness and disordered speech. CONCLUSIONS: These differences may represent increased risk of developing schizophrenia although their true significance will not be revealed until the cohort has been followed through the at-risk years.

Adult↗
PubMed1999

Ascertainment of a population of people with early-onset dementia in Lothian, Scotland.

OBJECTIVE: The aim of the case ascertainment for the study was to identify as near complete as possible a population of patients with presenile dementia who had been identified by hospital contact within a defined period of time, and who were currently alive, in the Lothian area. It did not aim to establish epidemiological figures. DESIGN: The Lothian Psychiatric Case Register was the main source of case identification. Case notes were inspected and cases identified for the study. SETTING: Patients were either in long-term care or at home. PATIENTS: As described in Paper I, Age range 30-65 years. MEASURES: Various diagnostic codings, including those of the ICD-9 were used to identify cases from the register. Feighner criteria were applied on case note inspection and DSM-III-R criteria after individuals had been seen. RESULTS: A potential of 557 cases were identified from the case register, etc. Of these, 431 were excluded and 126 seen for the study. CONCLUSIONS: The criteria used for inclusion and exclusion of cases in this study are thus directed towards achieving the aims of this study, and the findings would have to be modified to reach an estimate of all cases of early-onset dementia in the Lothian area.

Adult↗
PubMed1998

Effects of the M1 agonist xanomeline on processing of human beta-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells.

Complementary DNA (cDNA) encoding human beta-amyloid precursor protein familial Alzheimer's disease (FAD) Swedish mutant (beta APPSM) form was cloned into a mammalian expression vector (PK255) containing the CMV promoter. The vector was transfected into Chinese hamster ovary cells containing human muscarinic m1 receptors (CHO-m1), and clonal cells stably expressing beta APPSM were isolated. The effects of m1-receptor activation by the selective m1 agonist xanomeline and the non-selective muscarinic agonist carbachol on processing of beta APPSM to release soluble APP (APPs) and beta-amyloid peptide (A beta) were compared. Xanomeline stimulated APP release with a potency 1000-fold greater than that observed for carbachol. Concentrations of carbachol and xanomeline producing maximal effects on APPs release reduced the secretion of A beta by 28 and 46%, respectively. These results extend previous studies with xanomeline and suggest that cholinergic replacement therapy for Alzheimer's disease may reduce amyloid deposition.

Alzheimer Disease↗
PubMed1993

Synthesis of PCR-derived, single-stranded DNA probes suitable for in situ hybridization.

We report the novel synthesis of polymerase chain reaction (PCR)-derived single-stranded DNA (ssDNA) probes and their subsequent application in in situ hybridizations. Serial transverse sections of an 11.5-day postcoitum mouse embryo were hybridized to a 33P-ssDNA, 33P-RNA, or 35S-RNA probe corresponding to the same 181-bp sequence in the myogenin cDNA. Signal obtained using 33P-ssDNA was more intense than that using 33P-RNA probe, while signal/noise ratios obtained with both 33P-probes were far superior to those obtained with 35S-probe. Digoxigenin-labeled chicken growth hormone (GH) ssDNA gave slightly more intense signal than did digoxigenin-labeled chicken GH RNA when hybridized to chicken pituitary sections. 32P-ssDNA probes were found to be suitable for Northern blot hybridization. Advantages of using ssDNA probes for in situ hybridization include: (1) The ssDNA technique is rapid and simple. There was no need to clone a DNA template into a special RNA vector or order special T7-containing PCR primers. ssDNA probes can be synthesized in less than 1 day using any primers which currently exist in a laboratory (optimal probe length for in situ hybridization is between 50 and 200 bp). (2) In three separate in situ experiments, ssDNA probes yielded more intense signal than RNA probes. (3) ssDNA probes are potentially more stable than RNA probes. (4) Since the RNAse rinse is eliminated, posthybridization rinses are shortened when hybridizing with ssDNA probes. The ssDNA probes produced by this protocol can be labeled with a variety of different isotopes (both radioactive and nonradioactive), and are excellent probes for use in in situ hybridizations.

Animals↗
PubMed1992

Who benefits from electroconvulsive therapy? Combined results of the Leicester and Northwick Park trials.

This paper describes the results obtained by combining data from the Northwick Park and Leicester randomised controlled trials of ECT. Patients who suffered from depression in which retardation and delusions were features and who received real ECT had a significantly improved outcome at the end of four weeks of treatment (as measured by improvement in the HRSD) in comparison with those who received simulated ECT. However, this treatment effect was not detectable at six-month follow-up. Patients who were neither retarded nor deluded did not benefit significantly from real as opposed to simulated ECT.

Antidepressive Agents↗
PubMed1979

Possible virus in schizophrenia and some neurological disorders.

Cerebrospinal fluid from 13 of 38 patients with schizophrenia had a cytopathic effect in cultures of MRC5 cells. The cytopathic agent passed a 100 nm but not a 50 nm filter and was unaffected by heat at 56 degrees C for 30 min, treatment with chloroform, or the presence in cultures of bromodeoxyuridine. The agent could not be propagated serially in a satisfactory manner but its properties were those of a virus. A similar cytopathic effect was induced by cerebrospinal fluid from 8 of 11 patients with serious or chronic nervous system disease but only 1 of 25 patients with surgical or general medical conditions.

Adolescent↗
PubMedDate not supplied

Pain by numbers.

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Aged↗