Search PubMed⌕ Search

Biomedical subjects

G Plant

Publications and source records attributed to G Plant.

At least 19 recordsLinked to original sources
PubMed2006

Causes and outcomes for patients presenting with diplopia to an eye casualty department.

PURPOSE: To evaluate the causes and outcomes for patients presenting with diplopia to an eye casualty department. METHODS: Patients presenting with diplopia as a principal symptom, who were referred to the Orthoptic Department from Moorfields Eye Casualty over a 12-month period, were retrospectively investigated. RESULTS: One hundred and seventy-one patients were identified with complete records in 165 cases. There were 99 men and 66 women with an age range of 5-88 years. Monocular diplopia accounted for 19 cases (11.5%), whereas 146 patients (88.5%) had binocular diplopia. Cranial nerve palsies were the most common cause of binocular diplopia accounting for 98 (67%) of cases. Isolated sixth nerve palsy was the largest diagnostic group (n=45). Microvascular disease (hypertension or diabetes mellitus, or both) was present in 59% of patients with cranial nerve palsies, and of this group, 87% resolved spontaneously by 5 months rising to 95% by 12 months. CONCLUSION: Patients with clinically isolated single cranial nerve palsies associated with diabetes or hypertension are likely to recover spontaneously within 5 months and initially require observation only. However, patients with unexplained binocular diplopia and those who progress or fail to recover should be investigated to establish the underlying aetiology and managed as appropriate.

Adolescent↗
PubMed2006

Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study.

Molecular chaperons or amyloid-associated proteins (AAPs) are deposited in vascular and parenchymal amyloid lesions in Alzheimer's disease (AD) and other amyloidoses. AAPs, such as apolipoprotein E (ApoE) or apolipoprotein J (ApoJ) have been strongly implicated in the pathogenesis of AD in vitro and in vivo. Furthermore the possession of the ApoE in4 allele is a well-studied risk factor for AD. In view of the similarities between AD and both familial British dementia (FBD) and familial Danish dementia (FDD), we investigated the presence of AAPs in these two diseases to understand better their role in the general process of amyloidogenesis. Immunohistochemistry for ApoE, ApoJ, serum amyloid P (SAP), alpha-1-antichymotrypsin, cystatin C, heparan sulphate proteoglycans, such as agrin, perlecan, syndecans, glypican-1 and for heparan sulphate glycosaminoglycan (HS GAG) side chains was carried out together with immunohistochemical preparations specific to the amyloid subunits. Significant or extensive staining for ApoE, ApoJ, agrin, glypican-1 and HS GAG side chains was found in both amyloid (fibrillar) and preamyloid (nonfibrillar) deposits in FBD and FDD. The remaining AAPs, including SAP, were predominantly found in amyloid lesions. Only very weak staining was present in a small proportion of the amyloid lesions using perlecan immunohistochemistry. These findings suggest that the deposition patterns of AAPs in FBD and FDD are mostly similar to those in AD. The presence of AAPs in the preamyloid lesions supports the notion that chaperon molecules may play a role in the early steps of fibrillogenesis.

Alzheimer Disease↗
PubMed2006

Genetic alterations of the BRI2 gene: familial British and Danish dementias.

Classic arguments sustaining the importance of amyloid in the pathogenesis of dementia are usually centered on amyloid beta (Abeta) and its role in neuronal loss characteristic of Alzheimer disease, the most common form of human cerebral amyloidosis. Two non-Abeta cerebral amyloidoses, familial British and Danish dementias, share many aspects of Alzheimer disease, including the presence of neurofibrillary tangles, parenchymal pre-amyloid and amyloid deposits, cerebral amyloid angiopathy, and a widespread inflammatory response. Both early-onset conditions are linked to specific mutations in the BRI2 gene, causing the generation of longer-than-normal protein products and the release of 2 de novo created peptides ABri and ADan, the main components of amyloid fibrils in these inherited dementias. Although the molecular mechanisms and signal transduction pathways elicited by the amyloid deposits and their relation to cognitive impairment remain to be clarified, new evidence indicates that, independent of the differences in their primary structures, Abeta, ABri, and ADan subunits are able to form morphologically compatible ion-channel-like structures and elicit single ion-channel currents in reconstituted lipid membranes. These findings reaffirm the notion that non-Abeta amyloidosis constitute suitable alternative models to study the role of amyloid deposition in the mechanism of neuronal cell death.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Biopsy of resectable colorectal liver metastases causes tumour dissemination and adversely affects survival after liver resection.

BACKGROUND: Liver resection is increasingly being performed for metastatic colorectal cancer. This study assessed the need for preoperative biopsy of suspected metastases and whether biopsy has any effect on long-term survival. METHODS: Prospectively collected data on patients who underwent liver resection for colorectal metastases between 1986 and 2003 were reviewed retrospectively. The endpoints of morbidity, operative mortality and long-term survival were compared between patients who had biopsy before referral (group 1) and those who did not (group 2). RESULTS: Patient demographics and disease distribution were similar for 90 patients in group 1 and 508 in group 2. Seventeen patients (19 per cent) who had undergone biopsy either at the time of colorectal resection or radiologically had evidence of needle-track deposits. Operative mortality and morbidity rates in the two groups were similar. The 4-year survival rate after liver resection was 32.5 (s.e. 5.5) per cent in group 1, compared with 46.7 (2.8) per cent in group 2 (P = 0.008). CONCLUSION: Needle-track deposits are common after biopsy of suspected colorectal liver metastases. Biopsy of metastases confers poorer long-term survival on patients after liver resection and cannot be justified in patients with potentially resectable disease.

Biopsy, Needle↗
PubMed2005

Chromosome 13 dementias.

The importance of cerebral amyloid deposition in the mechanism of neurodegeneration is still debatable. Classic arguments are usually centered on amyloid beta(Abeta) and its role in the neuronal loss characteristic of Alzheimer's disease, the most common form of human cerebral amyloidosis. Two non-Abeta cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of Alzheimer's disease, including the presence of neurofibrillary tangles, parenchymal preamyloid and amyloid deposits, cerebral amyloid angiopathy and a variety of amyloid-associated proteins and inflammatory components. Both early-onset conditions are linked to specific mutations at or near the stop codon of the chromosome 13 gene BRI2 that cause generation of longer-than-normal protein products. Furin-like processing of these longer precursors releases two de novo-created peptides, ABri and ADan, which deposit as amyloid fibrils in FBD and FDD, respectively. Due to the similar pathology generated by completely unrelated amyloid subunits, FBD and FDD, collectively referred to as chromosome 13 dementias, constitute alternative models for studying the role of amyloid deposition in the mechanism of neuronal cell death.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.

Adult↗
PubMed2004

Tadpole pupil.

Explore the source record for details and available documents.

Adult↗
PubMed2001

Systemic amyloid deposits in familial British dementia.

Familial British dementia (FBD) is an early onset inherited disorder that, like familial Alzheimer's disease (FAD), is characterized by progressive dementia, amyloid deposition in the brain, and neurofibrillary degeneration of limbic neurons. The primary structure of the amyloid subunit (ABri) extracted from FBD brain tissues (Vidal, R., Frangione, B., Rostagno, A., Mead, S., Revesz, T., Plant, G., and Ghiso, J. (1999) Nature 399, 776-781) is entirely different and unrelated to any previously known amyloid protein. Patients with FBD have a single nucleotide substitution at codon 267 in the BRI2 gene, resulting in an arginine replacing the stop codon and a longer open reading frame of 277 amino acids instead of 266. The ABri peptide comprises the 34 C-terminal residues of the mutated precursor ABriPP-277 and is generated via furin-like proteolytic processing. Here we report that carriers of the Stop-to-Arg mutation have a soluble form of the amyloid peptide (sABri) in the circulation with an estimated concentration in the range of 20 ng/ml, several fold higher than that of soluble Abeta. In addition, ABri species identical to those identified in the brain were also found as fibrillar components of amyloid deposits predominantly in the blood vessels of several peripheral tissues, including pancreas and myocardium. We hypothesize that the high concentration of the soluble de novo created amyloidogenic peptide and/or the insufficient tissue clearance are the main causative factors for the formation of amyloid deposits outside the brain. Thus, FBD constitutes the first documented cerebral amyloidosis associated with neurodegeneration and dementia in which the amyloid deposition is also systemic.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Sequence, genomic structure and tissue expression of Human BRI3, a member of the BRI gene family.

The BRI3 gene is a member of the BRI gene family, made up of at least three different genes (BRI1-3). Previous studies established the cDNA sequence and structure of the human and mouse BRI1 and BRI2 genes and we recently reported that mutations in the BRI2 isoform, located on chromosome 13, are associated with dementia in humans. In the present work, we determine the complete cDNA sequence and genomic organization of the human BRI3 gene. BRI3 codes for a polypeptide of 267 amino acids, with a Mr of 30 KDa and a pI of 8.47. The amino acid sequence is 43.7% identical to the sequence of the human BRI2, and 38.3% identical to that of human BRI1, with the highest percentage of amino acid identity being concentrated on the C-terminal half of the molecules. In Northern blots, BRI3 cDNA hybridizes only one message of approximately 2.1 kilobases, which is predominantly present in the human brain. The BRI3 gene is localized on chromosome 2 and consists of six exons spanning more than 20 kb. Homology search of EST data banks retrieved a Caenorhabditis briggsae homolog of BRI, indicating that the BRI gene belongs to a strongly conserved gene family. These studies, aimed at characterizing the members of the BRI gene family, may provide valuable clues to the understanding of their normal function and how mutations in BRI2 can cause neurodegeneration and dementia similar to Alzheimer's disease.

Alternative Splicing↗
PubMed2001

Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia.

Familial British dementia (FBD), pathologically characterized by cerebral amyloid angiopathy (CAA), amyloid plaques, and neurofibrillary degeneration, is associated with a stop codon mutation in the BRI gene resulting in the production of an amyloidogenic fragment, amyloid-Bri (ABri). The aim of this study was to assess the distribution of ABri fibrillar and nonfibrillar lesions and their relationship to neurofibrillary pathology, astroglial and microglial response using immunohistochemistry, confocal microscopy, and immunoelectron microscopy in five cases of FBD. Abnormal tau was studied with immunoblotting. We present evidence that ABri is deposited throughout the central nervous system in blood vessels and parenchyma where both amyloid (fibrillar) and pre-amyloid (nonfibrillar) lesions are formed. Ultrastructurally amyloid lesions appear as bundles of fibrils recognized by an antibody raised against ABri, whereas Thioflavin S-negative diffuse deposits consist of amorphous electron-dense material with sparse, dispersed fibrils. In contrast to nonfibrillar lesions, fibrillar ABri is associated with a marked astrocytic and microglial response. Neurofibrillary tangles and neuropil threads occurring mainly in limbic structures, are found in areas affected by all types of ABri lesions whereas abnormal neurites are present around amyloid lesions. Immunoblotting for tau revealed a triplet electrophoretic migration pattern. Our observations confirm a close link between ABri deposition and neurodegeneration in FBD.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Chromosome 13 dementia syndromes as models of neurodegeneration.

Two hereditary conditions, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with amyloid deposition in the central nervous system and neurodegeneration. The two amyloid proteins, ABri and ADan, are degradation products of the same precursor molecule BriPP bearing different genetic defects, namely a Stop-to-Arg mutation in FBD and a ten-nucleotide duplication-insertion immediately before the stop codon in FDD. Both de novo created amyloid peptides have the same length (34 amino acids) and the same post-translational modification (pyroglutamate) at their N-terminus. Neurofibrillary tangles containing the classical paired helical filaments as well as neuritic components in many instances co-localize with the amyloid deposits. In both disorders, the pattern of hyperphosphorylated tau immunoreactivity is almost indistinguishable from that seen in Alzheimer's disease. These issues argue for the primary importance of the amyloid deposits in the mechanism(s) of neuronal cell loss. We propose FBD and FDD, the chromosome 13 dementia syndromes, as models to study the molecular basis of neurofibrillary degeneration, cell death and amyloid formation in the brain.

Amino Acid Sequence↗
PubMed2001

Familial cerebral amyloid angiopathy related to stroke and dementia.

The term cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the walls of leptomeningeal and cortical arteries, arterioles and, although less frequently in capillaries and veins. It is commonly associated with Alzheimers disease, Down's syndrome and normal aging, as well as with a variety of familial conditions related to stroke and/or dementia: hereditary cerebral hemorrhage with amyloidosis of Icelandic type (HCHWA-I), various inherited disorders linked to Abeta mutants (including the Dutch variant of HCHWA), and the recently described chromosome 13 familial dementia in British and Danish kindreds. This review focuses on four different types of hereditary CAA, emphasizing the notion that CAA is not only related to stroke but also to neurodegeneration and dementia of the Alzheimer's type.

Alzheimer Disease↗
PubMed2000

A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred.

Familial Danish dementia (FDD), also known as heredopathia ophthalmo-oto-encephalica, is an autosomal dominant disorder characterized by cataracts, deafness, progressive ataxia, and dementia. Neuropathological findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer's disease. N-terminal sequence analysis of isolated leptomeningeal amyloid fibrils revealed homology to ABri, the peptide originated by a point mutation at the stop codon of gene BRI in familial British dementia. Molecular genetic analysis of the BRI gene in the Danish kindred showed a different defect, namely the presence of a 10-nt duplication (795-796insTTTAATTTGT) between codons 265 and 266, one codon before the normal stop codon 267. The decamer duplication mutation produces a frame-shift in the BRI sequence generating a larger-than-normal precursor protein, of which the amyloid subunit (designated ADan) comprises the last 34 C-terminal amino acids. This de novo-created amyloidogenic peptide, associated with a genetic defect in the Danish kindred, stresses the importance of amyloid formation as a causative factor in neurodegeneration and dementia.

3' Untranslated Regions↗
PubMed2000

The use of tactile supplements in lipreading Swedish and English: a single-subject study.

The speech perception skills of GS, a Swedish adult deaf man who has used a "natural" tactile supplement to lipreading for over 45 years, were tested in two languages: Swedish and English. Two different tactile supplements to lipreading were investigated. In the first,"Tactiling," GS detected the vibrations accompanying speech by placing his thumb directly on the speaker's throat. In the second, a simple tactile aid consisting of a throat microphone, amplifier, and a hand-held bone vibrator was used. Both supplements led to improved lipreading of materials ranging in complexity from consonants in [aCa] nonsense syllables to Speech Tracking. Analysis of GS's results indicated that the tactile signal assisted him in identifying vowel duration, consonant voicing, and some manner of articulation categories. GS's tracking rate in Swedish was around 40 words per minute when the materials were presented via lipreading alone. When the lipreading signal was supplemented by tactile cues, his tracking rates were in the range of 60-65 words per minute. Although GS's tracking rates for English materials were around half those achieved in Swedish, his performance showed a similar pattern in that the use of tactile cues led to improvements of around 40% over lipreading alone.

Humans↗
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↗