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J Collinge

Publications and source records attributed to J Collinge.

At least 127 records · Page 7Linked to original sources
PubMed1991

Evidence for a pseudo-autosomal locus for schizophrenia using the method of affected sibling pairs.

A susceptibility locus for schizophrenia in the 'pseudo-autosomal' region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.

Alleles↗
PubMed1991

Decreased hippocampal expression of a glutamate receptor gene in schizophrenia.

'A striking and specific loss of the messenger RNA that encodes a non-N-methyl D-aspartate (non-NMDA) glutamate receptor was found in hippocampal tissue obtained at necropsy from 6 patients with schizophrenia, when compared to specimens from 8 controls without neurological or psychiatric signs or symptoms. These findings support suggestions of aberrant glutamatergic function in schizophrenia. Evidence that gene expression may be abnormal in schizophrenia, with decreased production of an excitatory neurotransmitter receptor, may have therapeutic as well as pathogenetic implications.'

Gene Expression Regulation↗
PubMed1991

Presymptomatic detection or exclusion of prion protein gene defects in families with inherited prion diseases.

The identification of defects in the prion protein (PrP) gene in families with inherited Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome allows presymptomatic diagnosis or exclusion of these disorders in subjects at risk. After counseling, PrP gene analysis was performed in three such individuals: two from families with a 144-bp insert and one with a point mutation at codon 102 in the PrP gene. The presence of a PrP gene defect was confirmed in one and excluded in two. Despite the potential problems of using PrP gene analysis in genetic prediction - specifically, uncertainty about penetrance and, generally, problems of presymptomatic testing in any inherited late-onset neurodegenerative disorder - we conclude that it has a role to play in improved genetic counseling for families with inherited prion diseases.

Adult↗
PubMed1990

Prion dementia without characteristic pathology.

Gerstmann-Sträussler syndrome (GSS) was diagnosed in a family with presenile dementia by prion protein gene analysis. Extensive histological examination of the brain of an affected individual from this family showed no characteristic features of GSS or Creutzfeldt-Jakob disease (CJD). Thus "spongiform encephalopathy" (GSS or CJD) cannot always be excluded on neuropathological grounds in an individual dying of a dementing condition, and the true prevalence of these diseases is likely to be underestimated. Screening by prion protein gene analysis will help to determine the full clinical and neuropathological phenotype in familial cases. This observation may be relevant to the assessment of possible transmission of bovine spongiform encephalopathy to man.

Alleles↗
PubMed1990

An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease.

In a pedigree with Creutzfeldt-Jakob disease we identified a 144-bp insertion in the open reading frame of the prion protein (PrP) gene. The insertion is in-frame and codes for 6 extra uninterrupted octapeptide repeats in addition to the 5 that are normally present in the N-terminal region of the protein. The possibility that this mutation may prove relevant to elucidating the mechanism of horizontal transmission of the spongiform encephalopathies is discussed.

Amino Acid Sequence↗
PubMed1989

Diagnosis of Gerstmann-Sträussler syndrome in familial dementia with prion protein gene analysis.

The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease. 2 members of a family in whom GSS was not previously suspected had a 0.15 kb insertion of similar size to that found in another kindred with pathologically proven spongiform encephalopathy. GSS may be more common than is currently realised; PrP gene analysis is potentially useful for diagnosis and genetic counselling in familial dementias and ataxias.

Adult↗
PubMed1987

Study of the action of cicletanine in hyperuricemic patients.

The possibility that the drug cicletanine might offer diuresis and reduction in plasma uric acid has been investigated in patients recruited from the rheumatology and general medical clinics. Nine hyperuricemic patients received cicletanine 100 mg daily by mouth for 21 days. Urinary clearance studies and plasma biochemistry were measured twice before treatment, twice at the start of treatment, and twice at the end of the treatment period. No change was observed in the urine volume, absolute or fractional excretion of sodium in response to the drug. There was no measurable change in the plasma uric acid or urinary urate clearance. Creatinine clearance and potassium excretion also remained constant. No adverse effects were observed apart from a possibly drug-related elevation in serum aspartate amino transferase in one patient. The study provides no support for the postulated diuretic or hypouricemic effects of the drug.

Adult↗
PubMed1986

Family support system in newborn medicine: does it work? Follow-up study of infants at risk.

Acute illness in early childhood generates chronic anxiety in parents, which may manifest itself in part by inappropriate use of health care. To minimize this and the development of other psychosocial sequelae associated with neonatal illness, a family support system (FSS) was developed and implemented in a neonatal intensive care unit. The effectiveness of the FSS was assessed by the evaluation of emergency room and inpatient hospital service utilization in 80 patients born before, and 90 patients born after the institution of the program. At the outset, the groups had similar medical and social characteristics. There was no difference between the two groups in the utilization of emergency services in the first year after discharge. However, during the second year the control group used the emergency room twice as often as the study group did (P less than 0.025). During the first 2 years, half of the control group was readmitted, compared with less than a third of the study group (P less than 0.005). Overall, after discharge from the neonatal intensive care unit the control group spent an average of 9 days per patient in hospital, compared with a mean of 3 days per patient in the study group (P less than 0.025). It appears, therefore, that the FSS may be an effective way to reduce some of the psychosocial sequelae of illness in newborn infants requiring intensive care.

Adolescent↗
PubMed1983

Studies on the interaction between cerebral 5-hydroxytryptamine and gamma-aminobutyric acid in the mode of action of diazepam in the rat.

The effect of the benzodiazepine, diazepam, administered for 7 days in doses between 1.25 and 5 mg kg-1 was studied on the turnover of 5-hydroxytryptamine (5-HT) in rat cerebral cortex. 5-HT turnover was assessed by calculating the ratio of the concentration of the major metabolite 5-hydroxyindoleacetic acid (5-HIAA) to that of 5-HT (i.e., 5-HIAA:5-HT). Diazepam (2.5 and 5 mg kg-1 i.p. daily for 7 days) significantly reduced cerebral cortical 5-HT turnover. The effect of manipulating cerebral gamma-aminobutyric acid (GABA) mechanisms on this action of diazepam was studied. Treatment of animals with a subconvulsive dose of picrotoxin (3 mg kg-1 i.p.) reversed the fall in cortical 5-HT turnover seen following diazepam. In contrast, however, treatment with the GABA transaminase inhibitors, amino-oxyacetic acid (25 mg kg-1) or ethanolamine-O-sulphate (250 mg kg-1, 7 days) which elevated cerebral GABA concentrations, enhanced the reduction in cortical 5-HT turnover following diazepam. Focal injection of picrotoxin (0.1 micrograms) into the region of the dorsal raphé nucleus reversed the decrease in cortical 5-HT turnover caused by diazepam. The hypothesis that doses of diazepam which result in total plasma concentrations comparable to those observed in man produce a reduction in 5-HT turnover mediated via GABA neurones is discussed.

Aminobutyrates↗
PubMed1982

Differential actions of diazepam on the release of [3H]5-hydroxytryptamine from cortical and midbrain raphe slices in the rat.

The possible interaction of the benzodiazepine diazepam with synaptic mechanisms of the central neurotransmitter 5-hydroxytryptamine (5-HT) has been studied in the rat using the superfusion in vitro release technique. The effect of diazepam (1-100 microM) on the spontaneous and potassium-induced release of radioactivity from superfused slices preloaded with [3H]5-HT prepared from cerebral cortex (fronto-parietal) and midbrain raphe region was monitored and compared. The results demonstrate a differential action of diazepam on the release of cortical and raphe 5-HT. In cerebral cortex diazepam significantly reduces both spontaneous and potassium-evoked release of [3H]5-HT. Conversely in raphe slices diazepam significantly enhances both spontaneous and potassium-evoked release of [3H]5-HT. In both tissues the effect of diazepam on K+-stimulated neurotransmitter release was abolished in the presence of picrotoxin. The experiments suggest that the effects of benzodiazepines on 5-HT mechanisms may be manifested at least in part through gamma-aminobutyric acid receptors.

Animals↗
PubMed1981

The effect of varying protein quality and energy intake on the nitrogen metabolism of parenterally fed very low birthweight (less than 1600 g) infants.

Net nitrogen retention (NNR) and rates of whole-body protein turnover (Q), synthesis, and breakdown (B) were measured in 24 intravenously fed premature infants, birthweight less than 1600 g, at the end of the first week of life. Four regimes were used: Amigenglucose +/- Intralipid; Vamin-glucose +/- Intralipid. Mean protein intake was 2.7 g/kg/day. Mean energy intakes were 68 to 98 kcal/kg/day. Vamin was a better protein source (p less than 0.01), evidence by a higher NNR; 72 +/- 2%, cf. 56 +/- 4% at high-energy intakes. The high-energy intake also improved (p less than 0.01) protein retention (NNR); 64 cf. 50%. Infants receiving 2.9 g of Vamin (394 mg N)/ kg/day and 85 kcal/kg/day of nonprotein intake retained nitrogen at intrauterine rates (282 +/- 7 mg/kg/day). Diet had no effect on Q, synthesis, or B. However, the protein source had a significant effect (p less than 0.01) on the fraction of N-flux coming from protein breakdown (B/Q); 71.7% for Vamin, cf. 77.1% for Amigen. Similarly, energy intake had a significant effect (p less than 0.01) on the fraction N-flux utilized for protein synthesis (S/Q); 91.3% high energy cf. 87.0% low energy. These results suggest that an increased energy intake improved N-retention by enhancing amino acid reutilization for protein synthesis, whereas a higher quality protein improved N-retention by limiting protein breakdown..3% high energy cf. 87.0% low energy. These results suggest that an increased energy intake improved N-retention by enhancing amino acid reutilization for protein synthesis, whereas a higher quality protein improved N-retention by limiting protein breakdown..3% high energy cf. 87.0% low energy. These results suggest that an increased energy intake improved N-retention by enhancing amino acid reutilization for protein synthesis, whereas a higher quality protein improved N-retention by limiting protein breakdown.

Diet↗