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Biomedical subjects

S Mead

Publications and source records attributed to S Mead.

At least 19 recordsLinked to original sources
PubMed2003

Phenotypic variability in the brains of a family with a prion disease characterized by a 144-base pair insertion in the prion protein gene.

The use of prion protein (PrP) immunohistochemistry in neuropathology has allowed identification of prion diseases with otherwise atypical histological features. The brains from family members with familial prion diseases can show marked histological variation. A histological and immunohistochemical study was performed on 10 brains of patients with a familial prion disease caused by a 144-base pair (bp) insertion in the prion protein gene. The histology from the cases showed variability in the severity of spongiform change and astrocytosis in both the cerebellum and the cerebrum. There was also variability in the density of microglial cells. The PrP immunohistochemistry revealed that in nine cases there was a similar patch-like deposition of PrP within the molecular layer of the cerebellum. Although in the cerebellum there did seem to be some correlation between the severity of spongiform change, astrocytosis and the density of microglial cells, there was no such correlation between any of these three parameters and the density of PrP staining. There was deposition of beta-amyloid precursor protein (beta-APP) in the cerebellum, suggesting that disrupted axonal transport had a possible role in the evolution of the disease. The cases illustrate the histological variability that can occur in familial prion diseases despite similarity in PrP staining. They also reveal that the relationship between PrP deposition and cerebral or cerebellar damage might be complex.

Adult↗
PubMed2001

Sporadic--but not variant--Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1.

Human prion diseases have inherited, sporadic, and acquired etiologies. The appearance of the novel acquired prion disease, variant Creutzfeldt-Jakob disease (vCJD), and the demonstration that it is caused by the same prion strain as that causing bovine spongiform encephalopathy, has led to fears of a major human epidemic. The etiology of classical (sporadic) CJD, which has a worldwide incidence, remains obscure. A common human prion-protein-gene (PRNP) polymorphism (encoding either methionine or valine at codon 129) is a strong susceptibility factor for sporadic and acquired prion disease. However, a quantitative-trait-locus study of prion incubation periods in mice has demonstrated an important factor that is close to Prnp but is independent of its coding sequence or that of the nearby prion-like doppel gene (Prnd). We have analyzed the PRNP locus for such tightly linked susceptibility factors. Fifty-six polymorphic sites have been identified within 25 kb of the PRNP open reading frame, including sites within the PRNP promoter and the PRNP 3' untranslated region. These have been characterized in 61 Centre d'Etude du Polymorphisme Humain (CEPH) families, demonstrating extensive linkage disequilibrium around PRNP and the existence of 11 major European PRNP haplotypes. Haplotype frequencies estimated in healthy U.K. control individuals were very similar to those deduced in the CEPH families. A common haplotype was overrepresented in patients with sporadic CJD (sCJD). Through use of a log-linear modeling approach to simultaneously model Hardy-Weinberg and linkage disequilibria, a significant independent association was found between sCJD and a polymorphism upstream of PRNP exon 1 (P=.005), in addition to the strong susceptibility conferred by codon 129 (P=2x10(-8)). However, although our sample size was necessarily small, no association was found between these polymorphisms and vCJD or iatrogenic CJD, in keeping with their having distinct disease mechanisms. In addition, there was no evidence of a PRNP founder effect in the first reported geographical cluster of vCJD.

3' Untranslated Regions↗
PubMed2001

Two-octapeptide repeat deletion of prion protein associated with rapidly progressive dementia.

Insertions of integral numbers of an octapeptide repeat in the prion protein gene are pathogenic mutations associated with inherited prion diseases. Conversely, deletions of a single octapeptide repeat are found as normal polymorphisms in many populations and do not predispose individuals to prion disease. The authors report a two-octapeptide repeat deletion in an elderly woman with a rapidly progressive dementia consistent with Creutzfeldt-Jakob disease. This mutation was absent from more than 3,000 individuals and may be causally related to prion disease and represent a novel disease mechanism.

Aged↗
PubMed2001

Peer support: a theoretical perspective.

This article offers one theoretical perspective of peer support and attempts to define the elements that, when reinforced through education and training, provide a new cultural context for healing and recovery. Persons labeled with psychiatric disability have become victims of social and cultural ostracism and consequently have developed a sense of self that reinforces the "patient" identity. Enabling members of peer support to understand the nature and impact of these cultural forces leads individuals and peer communities toward a capacity for personal, relational, and social change. It is our hope that consumers from all different types of programs (e.g. drop-in, social clubs, advocacy, support, outreach, respite), traditional providers, and policy makers will find this article helpful in stimulating dialogue about the role of peer programs in the development of a recovery based system.

Humans↗
PubMed2001

The use of volume standards in health services.

The ways in which volume standards are implemented by health services organizations are not clear. Therefore, the authors sought to evaluate the extent of use of volume standards, the purposes for which such standards were developed, and the sources of the standards in a sample of health services organizations. The authors found that volume standards were used widely by accrediting organizations, professional societies, and hospitals in their sample, but almost never by health maintenance organizations. Volume standards were used for ensuring adequate experience among residents, providing guidelines to residency programs, and privileging and credentialing physicians. Expert consensus appeared to be the usual source of volume standards.

Accreditation↗
PubMed2000

Examination of the human prion protein-like gene doppel for genetic susceptibility to sporadic and variant Creutzfeldt-Jakob disease.

A novel human gene named Doppel (DPL) that has homology to the prion protein gene (PRNP) has recently been identified on chromosome 20p. By automated sequencing we have found a common (M174T, 48%) and an uncommon coding polymorphism. The polymorphic frequency of the M174T allele was examined in cases of variant and sporadic Creutzfeldt-Jakob Disease and compared with the frequency in the normal UK population. In sharp distinction to the M129V polymorphism of PRNP we have not found any evidence of disease association nor is there any association with age of onset, disease duration, or prion protein (PrP(Sc)) strain type.

Chromosomes, Human, Pair 20↗
PubMed2000

What recovery means to us: consumers' perspectives.

In this article two consumer leaders use their own experiences to explain the meaning and significance of recovery. They emphasize the importance of hope, personal responsibility, education, advocacy, and peer support. They also address controversial issues, such as the nature of the therapeutic relationship, the place of medications in symptom control, and the need for attitudinal changes in mental health professionals.

Attitude of Health Personnel↗
PubMed2000

Familial British dementia with amyloid angiopathy: early clinical, neuropsychological and imaging findings.

Familial British dementia with amyloid angiopathy (FBD) is an autosomal dominant condition characterized by a dementia, progressive spastic tetraparesis and cerebellar ataxia with onset in the sixth decade. A point mutation in the BRI gene has been shown to be the genetic abnormality. Genealogical work with the large family originally reported by Worster-Drought and updated by Plant has identified nine generations dating back to the late eighteenth century. The pedigree now includes six living affected patients, 35 historical cases, and 52 descendants at risk of having inherited the disease. A common ancestor has been identified between the large pedigree and a case report of 'familial cerebellar ataxia with amyloid angiopathy'. An autopsy case from a separate family with an identical condition is described but no common ancestor with the large pedigree has been found. Case histories have been researched and updated in each pedigree. Eleven individuals at risk of FBD, aged between 44 and 56 years, agreed to undergo a clinical and neuropsychological assessment along with MRI brain imaging in order to clarify early diagnostic features. Five of the eleven were thought to show early clinical signs of the disease. Neurological examination was abnormal in three, with limb and gait ataxia and mild spastic paraparesis. Three had impaired recognition and recall memory and another had mild impairment of delayed visual recall. All affected individuals had an abnormal MRI of the brain, consisting of deep white-matter hyperintensity (T(2)-weighted scans) and lacunar infarcts, but no intracerebral haemorrhage. The corpus callosum was affected particularly, and in one patient it was severely atrophic.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A newly formed amyloidogenic fragment due to a stop codon mutation causes familial British dementia.

Familial British dementia (FBD) is an early-onset autosomal dominant disorder characterized by progressive cognitive impairment, spasticity, and cerebellar ataxia. Hippocampal neurofibrillar degeneration and widespread parenchymal and vascular amyloid deposits are the main neuropathological lesions. Amyloid fibrils are composed of a novel 34 amino acid subunit (ABri) with no sequence identity to any known amyloid molecule. The peptide derives from a larger precursor protein codified by a single gene BRI on chromosome 13. Affected family members have a single base substitution at the stop codon of the BRI gene that generates a longer open-reading frame resulting in a larger precursor protein. The release of the 34 C-terminal amino acids from the mutated precursor originates the ABri amyloid subunit. Our discovery of a new amyloid associated with the development of dementia supports the concept that amyloid peptides may be of primary importance in the initiation of neurodegeneration.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13.

Familial British dementia (FBD) is a disorder characterized by the presence of amyloid deposits in cerebral blood vessels and brain parenchyma coexisting with neurofibrillary tangles in limbic areas. The amyloid subunit (ABri) is a 4 kDa fragment of a 266 amino acid type II single-spanning transmembrane precursor protein encoded by the BRI gene located on chromosome 13. In FBD patients, a single base substitution at the stop codon of this gene generates a larger 277-residue precursor (ABriPP-277). Proteolytic processing by a furin-like enzyme at the C-terminus of the elongated precursor generates the 34 amino acid ABri that undergoes rapid aggregation and fibrillization. ABri is structually unrelated to all known amyloids including A beta, the main component of the amyloid lesions in Alzheimer's disease (AD), indicating that cerebral deposition of amyloid molecules other than A beta can trigger similar neuropathological changes leading to neuronal loss and dementia. These data support the concept that amyloid deposition in the vascular wall and brain parenchyma is of primary importance in the initiation of neurogeneration.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Recovery-oriented psychopharmacology: redefining the goals of antipsychotic treatment.

The traditional goals of psychopharmacology stem from the medical model. Rehabilitation interventions attempt to improve aspects of functioning in patients with chronic illnesses that are not responsive to biological intervention. Recovery is a concept emanating from the consumer self-help movement. It describes a move away from the patient role defined by a diagnostic label toward community membership defined by relationships and responsibilities in the community. Comprehensive care for people with psychotic disorders can include attention to each realm. This article provides an overview of the 3 models of care and describes a role for the psychopharmacologist in each as well as his or her unique potential to incorporate all 3. We outline potential synergistic benefits of integrating recovery-, rehabilitation-, and medical-model thinking into the practice of psychopharmacology and explore implications for the goals and outcomes of treatment for people with psychotic disorders.

Adaptation, Psychological↗
PubMed1999

A stop-codon mutation in the BRI gene associated with familial British dementia.

Familial British dementia (FBD), previously designated familial cerebral amyloid angiopathy-British type, is an autosomal dominant disorder of undetermined origin characterized by progressive dementia, spasticity, and cerebellar ataxia, with onset at around the fifth decade of life. Cerebral amyloid angiopathy, non-neuritic and perivascular plaques and neurofibrillary tangles are the predominant pathological lesions. Here we report the identification of a unique 4K protein subunit named ABri from isolated amyloid fibrils. This highly insoluble peptide is a fragment of a putative type-II single-spanning transmembrane precursor that is encoded by a novel gene, BRI, located on chromosome 13. A single base substitution at the stop codon of this gene generates a longer open reading frame, resulting in a larger, 277-residue precursor. Release of the 34 carboxy-terminal amino acids from the mutated precursor generates the ABri amyloid subunit. The mutation creates a cutting site for the restriction enzyme XbaI, which is useful for detecting asymptomatic carriers. Antibodies against the amyloid or homologous synthetic peptides recognize both parenchymal and vascular lesions in FBD patients. A point mutation at the stop codon of BRI therefore results in the generation of the ABri peptide, which is deposited as amyloid fibrils causing neuronal disfunction and dementia.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Measuring skill acquisition and retention with an ATM simulator: the need for age-specific training.

The present study focused on the type of information presented during training and its effects on initial and retention performance of older and younger adults interacting with computerized, new technology. The effects of emphasizing concepts versus actions during training on performance immediately after training and after a 1-month retention interval were examined. Younger and older adults completed either action or concept training for operating a virtual automatic teller machine (ATM). Overall, action training was associated with faster and more accurate performance immediately after training and better retention performance for older adults. For older adults, value of type of training interacted with type of task component. These findings are applicable to the development of age-specific training materials for computerized tasks.

Adolescent↗
PubMed1995

Identification of YAC clones for human chromosome 1p32 and physical mapping of the infantile neuronal ceroid lipofuscinosis (INCL) locus.

Infantile neuronal ceroid lipofuscinosis (INCL, CLN1) is a neurodegenerative disorder in which the biochemical defect is unknown. We earlier assigned the disease locus to chromosome 1p32 in the immediate vicinity of the highly informative HY-TM1 marker by linkage and linkage disequilibrium analysis. Here we report the construction of PFGE maps on the CLN1 region covering a total of 4 Mb of this relatively poorly mapped chromosomal region. We established the order of loci at 1p32 as tel-D1S57-L-myc-HY-TM1-rlf-COL9A2-D1S193-D1S6 2-D1S211-cen by combining data obtained from analysis of a chromosome 1 somatic cell hybrid panel, PFGE, and interphase FISH. We isolated YACs and constructed two separate YAC contigs, the loci L-myc, HY-TM1, rlf, and COL9A2 being present on a 1000-kb contig and the markers D1S193, D1S62, and D1S211 on a YAC contig spanning a maximum of 860 kb. Within the 1000-kb contig we were able to identify five CpG islands in addition to those associated with the earlier cloned genes. The YAC contigs as well as the physical map provide us with tools for the identification of the INCL gene.

Base Sequence↗
PubMed1994

Assignment of sterol carrier protein X/sterol carrier protein 2 to 1p32 and its exclusion as the causative gene for infantile neuronal ceroid lipofuscinosis.

In the positional cloning of a disease gene with an unknown protein defect a spectrum of molecular biological methods is applied after linkage has been established. It is reasonable to analyze in detail any relevant candidate gene mapping to the particular chromosomal region. We report here the refined chromosomal assignment of SCPx/SCP2, a gene coding for the protein that is believed to have an important role in lipid metabolism by transporting many kinds of lipid molecules between organelles. This gene represents an excellent candidate gene for infantile neuronal ceroid lipofuscinosis, earlier assigned to 1p32 by us, since lipid metabolism in the patient's brain appears to be significantly disturbed. Expression and structural analyses by Northern, Southern and Western blotting as well as SSCP and direct sequencing did not detect any differences between the cDNAs of patients and controls. Consequently, it is unlikely that a mutation in SCPx/SCP2 is the underlying cause of this severe neurodegenerative disease of childhood.

Acetyl-CoA C-Acetyltransferase↗
PubMed1992

A nonphotic stimulus causes instantaneous phase advances of the light-entrainable circadian oscillator of the Syrian hamster but does not induce the expression of c-fos in the suprachiasmatic nuclei.

The study investigated whether nonphotic cues that alter the phase of overt circadian rhythms do so by causing instantaneous shifts in the underlying, light-sensitive clock. Wheel-running activity in Syrian hamsters was studied under free-running conditions of constant dim red light as an overt marker of circadian phase, the daily onset of activity being defined as circadian time 12 (CT 12). Exposure to a 15 min pulse of bright light at CT 12.20 caused a phase delay in activity onset, whereas pulses delivered at CT 11.20 had no effect upon the overt rhythm. Correlated with their effect on behavior, light pulses delivered at CT 12.20 induced expression of c-fos-like immunoreactivity in the retinorecipient regions of the suprachiasmatic nuclei of the hypothalamus (SCN), whereas pulses delivered at CT 11.20 had no effect upon the expression of c-fos. Expression of this immediate-early gene therefore provided a second marker of circadian phase, because its induction by light is closely correlated with the onset of subjective night (CT 12). To establish a suitable protocol for nonphotic shifts of the activity rhythm, animals were handled and received a subcutaneous injection of saline at different circadian phases. Injections at CT 8 or CT10 caused an immediate bout of wheel-running activity, and a consequent phase advance in the activity rhythm as assessed by the earlier onsets of activity in successive days. Handling and injections at other circadian phases were without effect. Despite shifting the overt rhythm, these procedures at CT 10 did not lead to the expression of c-fos in the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗