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G Glover

Publications and source records attributed to G Glover.

At least 19 recordsLinked to original sources
PubMed2006

[Hereditary pancreatitis caused by a new mutation in the trypsinogen gene. Report of a family].

Hereditary pancreatitis is an uncommon autosomal dominant disease secondary to a mutation normally located in the trypsinogen gene, preventing trypsin deactivation. This mutation translates clinically into recurrent attacks of acute pancreatitis and an increased risk of pancreatic cancer. We report a case of acute hereditary pancreatitis due to a trypsinogen mutation that has previously been described in only one family.

Child↗
PubMed2005

Motifs that mediate dendritic targeting in hippocampal neurons: a comparison with basolateral targeting signals.

One model for dendritic protein sorting in neurons is based on parallels with basolateral targeting in Madin-Darby Canine Kidney (MDCK) epithelial cells. The goal of this study was to further evaluate this model by analyzing the neuronal targeting of several proteins that contain well-defined basolateral sorting motifs. When we expressed FcRgammaII-B2 and CD44, two basolateral markers whose sorting depends on dihydrophobic motifs, they were unpolarized in hippocampal neurons. We also assessed the localization of the Epidermal Growth Factor Receptor (EGFR), a basolateral protein whose sorting signal contains a proline-rich motif and two dihydrophobic motifs. EGFR was restricted to the dendrites in neurons and relied on the same sorting signal for proper targeting. These results show that the dendritic sorting machinery in neurons does not recognize dihydrophobic-based basolateral sorting signals. In contrast, the sorting signal present in EGFR directs both basolateral and dendritic targeting and defines a novel dendritic targeting motif.

Amino Acid Motifs↗
PubMed2004

Novel HMBS founder mutation and significant intronic polymorphism in Spanish patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis, caused by a partial deficiency of hydroxymethylbilane synthase (HMBS). Knowledge of the nature of the HMBS mutations causing AIP in Spanish families is very limited. Here we report a novel 669_698del of the HMBS gene in twenty-two individuals from five independent Spanish AIP families, settled in Murcia (southeastern region of Spain). All mutation carriers shared a common disease associated haplotype indicating an ancestral founder effect. Identification of the 669_698del founder mutation allowed rapid and simple molecular diagnosis of AIP in families from this region in Spain. In addition, 771 + 58C>T in intron 12 on the non-669_698del allele was identified in six AIP patients, which promoted homozygous AIP misdiagnosis.

Adult↗
PubMed2003

Dissociated neural representations of intensity and valence in human olfaction.

Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.

Adult↗
PubMed2003

Diagnosis and treatment of oculopharyngeal dystrophy: a report of three cases from the same family.

Oculopharyngeal muscular dystrophy is a hereditary pathology transmitted in an autosomal dominant manner. The clinical symptoms are palpebral ptosis, oropharyngeal dysphagia and proximal limb weakness. Upper gastro-esophageal endoscopy is recommended to study the dysphagia, a video-radiology study with barium and an esophageal manometry to study the pharyngeo-esophageal motor disorder. Muscle biopsy reveals the presence of atrophic fibers substituted by an increase in fat and connective tissue. In 1998 Brais described the genetic alteration responsible for this pathology, a limited expansion of the triplet of GCG nucleotides in PABP2 gene on chromosome 14q11. Normal individuals have the homozygotic form (GCG)6 of this triplet, whereas patients with the described syndrome have the heterozygotic form (GCG)6-(GCG)9 or (GCG)6-(GCG)10. We present three siblings from the same family with diagnoses and genetic confirmations of oculopharyngeal dystrophy. Two of the patients underwent cricopharyngeal myotomy to relieve the dysphagia.

Aged↗
PubMed2003

Incidence of fragile X in 5,000 consecutive newborn males.

Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation in males. Even though this affirmation is repeated in virtually all papers referring to FXS, the precise frequency of this syndrome in the general population is unknown. We present a general population screening analyzing an anonymous series of 5,000 consecutive newborn males from the neonatal screening program of the population of Catalonia in Spain. The aim of the study is to determine the incidence of FXS via a simple and economical methodology based on the nonamplification of the fragment containing the CGG repeats of the FRAXA locus in the samples carrying alleles over 52 repeats. From the initial 5,000 samples, 4,920 were in the normal range, 15 gave rise to bands with more than 52 repeats (11 corresponded to intermediate alleles and four premutated alleles). After further studies, two samples were considered to be carriers of full mutations. According to these results, the incidence of FXS affected newborn males is 1 in 2,466, and 1 in 1,233 males is a carrier of the premutation. We can deduce that 1 in 8,333 is an affected female with clinical manifestations and 1 in 411 will be a premutation carrier woman. Upon reviewing the literature, there seems to be variability in the frequencies found by the different groups. Therefore, given that our study is limited to the Catalan population in Spain, these results should be taken as valid for the Catalan region and should only be extrapolated to other populations with caution.

Fragile X Messenger Ribonucleoprotein 1↗
PubMed2001

Regulation of DNA binding and trans-activation by a xenobiotic stress-activated plant transcription factor.

As-1-type cis-elements augment transcription of both nuclear and pathogen genes in response to stress and defense cues in plants. Basic/leucine zipper proteins termed "TGA factors" that specifically bind as-1 elements are likely candidates for mediating these transcription activities. Our earlier work has shown that 2, 4-dichlorophenoxyacetic acid-induced xenobiotic stress enhances trans-activation by a chimeric fusion protein of the yeast Gal4 binding domain and TGA1a, a TGA factor of tobacco. Here we demonstrate that xenobiotic stress also enhances the ability of native TGA1a to bind as-1 and activate transcription of a known target gene. In addition, the previously identified xenobiotic stress-responsive domain of TGA1a was found to inhibit this factor's trans-activation potential by a mechanism that appears to involve stimulus-reversible interactions with a nuclear repressor protein. Results from these and other studies can now be placed in the context of a working model to explain basal and xenobiotic stress-induced activities of TGA1a through its cognate cis-acting element.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

[Diagnosis of fragile X syndrome].

The fragile X syndrome (FXS) is the main cause of hereditary mental retardation. Although a lower frequency has been demonstrated in latest population studies, FXS constitutes the most frequent cause of hereditary mental retardation. FXS was historically diagnosed, firstly, only in clinically affected patients, but it was not possible to detect carriers with no symptoms. Once the mechanisms that specifically induced X chromosomal fragility were beginning to be understood, it became possible to confirm clinically diagnosed patients and detect some of asymptomatic carriers. But, the discovery of FMR1 gene has allowed us to reliable know the genetic status of anyone with respect to fragile X syndrome, independently of whether one belongs to a fragile X family. In this respect a combination of molecular and cytogenetic techniques may be used to detect expansions in the repeat region of the FMR1 gene. Three classes of alleles are found, normal with 5-60 repeats, premutated with repeats between 60 and 200 copies and full mutated with expansion greater than 200 copies.

Alleles↗
PubMed2000

Expenditure on mental health care by English health authorities: a potential cause of inequity.

BACKGROUND: The York resource allocation formula includes a calculation of the amount needed to purchase mental health services equitably in each health authority in England. However, the amount which is actually spent on services is at the discretion of the authority. AIMS: To compare expenditure on mental health services with allocation, and test the hypothesis that differences between them are to the disadvantage of services in deprived areas. METHOD: A comparison of routine expenditure and allocation data, and linear regression modelling of the ratio of expenditure to allocation. RESULTS: The ratio of expenditure to allocation varies widely. Relative underspending occurs more frequently in deprived areas, although not in the four inner-London health authorities. CONCLUSIONS: The intentions of the York formula are not achieved in practice. The implications of the formula for mental health should be made explicit to health authorities, and shortfalls in mental health expenditure relative to allocation should be justified at a local level.

Costs and Cost Analysis↗
PubMed1999

Outcome of long stay psychiatric patients resettled in the community: prospective cohort study.

OBJECTIVE: To examine the outcome of a population of long stay psychiatric patients resettled in the community. DESIGN: Prospective study with 5 year follow up. SETTING: Over 140 residential settings in north London. SUBJECTS: 670 long stay patients from two London hospitals (Friern and Claybury) discharged to the community from 1985 to 1993. MAIN OUTCOME MEASURES: Continuity and quality of residential care, readmission to hospital, mortality, crime, and vagrancy. RESULTS: Of the 523 patients who survived the 5 year follow up period, 469 (89.6%) were living in the community by the end of follow up, 310 (59.2%) in their original community placement. A third (210) of all patients were readmitted at least once. Crime and homelessness presented few problems. Standardised mortality ratios for the group were comparable with those reported for similar populations. CONCLUSIONS: When carefully planned and adequately resourced, community care for long stay psychiatric patients is beneficial to most individuals and has minimal detrimental effects on society.

Adult↗
PubMed1999

A FAIR study of motor cortex activation under normo- and hypercapnia induced by breath challenge.

In this study an arterial spin-tagging technique based on flow-sensitive alternating inversion recovery (FAIR) with single-shot spiral data acquisition was used to study how the basal cerebral blood flow (CBF) elevated by breath holding affects the regional cerebral blood flow (rCBF) response to focal brain activation in the motor cortex. Six subjects were examined using three types of activation studies. These were (a) bilateral finger tapping paced at 4 Hz under normal breathing, (b) repeated expiration breath holding of 30 s, and (c) simultaneous breath holding and finger tapping. It was found that in five of six subjects the prevailing CBF level adjusted by breath challenge and the increase in rCBF in motor cortex associated with bilateral finger tapping were completely additive. This finding from FAIR-based functional magnetic resonance imaging is in accordance with that reported from published positron emission tomography studies. The results indicate that in the majority of the subjects examined the regulatory mechanisms for vasodilatory reaction to CO(2) and rCBF response to neural activation in motor cortex region are independent.

Adult↗
PubMed1999

The feasibility of routine outcome measures in mental health.

BACKGROUND: Standardised outcome measures are not being used in routine mental health care. METHOD: The importance of routine use of standardised outcome measures is argued, and reasons for their lack of use suggested. RESULTS: One reason for standardised outcome measures not being used routinely is the lack of appropriate instruments. This property of being suitable for routine use is often called feasibility, but there is no consensus about the meaning of feasibility, or how it should be measured. We propose a definition of feasibility as a psychometric property of a standardised outcome measure, provide criteria for assessing feasibility, and then present a framework for changing practice to increase the routine use of standardised outcome measures. CONCLUSIONS: If mental health care is to maximise outcome, then more attention needs to be paid both to the process of developing and to facilitating the routine clinical use of feasible outcome measures.

Feasibility Studies↗
PubMed1999

Evaluating mental health policy in England. Care Programme Approach and supervision registers.

BACKGROUND: The Care Programme Approach (CPA) and supervision register policies in England are intended to prioritize patients to receive specialist mental health care. AIMS: To describe and evaluate the practical application of the policies. METHOD: A questionnaire survey of key informants in mental health provider trusts and an analysis of aggregated data collected by health authorities using the Mental Illness Needs Index as a measure of population need. RESULTS: On average, 1175 per 100,000 total population are subject to the CPA (95% CI = 1055-1309) and 8.6 per 100,000 (95% CI = 7.5-9.9) are on supervision registers. Wide local variations in the number of people subject to the CPA and supervision registers are not explained by variations in population need. CONCLUSIONS: Prioritization to receive specialist mental health services is carried out inconsistently, and inequitable use of resources may result.

Community Mental Health Services↗
PubMed1998

Hemispheric asymmetry for emotional stimuli detected with fMRI.

Current brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.

Adult↗
PubMed1998

Sporadic imprinting defects in Prader-Willi syndrome and Angelman syndrome: implications for imprint-switch models, genetic counseling, and prenatal diagnosis.

The Prader-Willi syndrome (PWS) and the Angelman syndrome (AS) are caused by the loss of function of imprinted genes in proximal 15q. In approximately 2%-4% of patients, this loss of function is due to an imprinting defect. In some cases, the imprinting defect is the result of a parental imprint-switch failure caused by a microdeletion of the imprinting center (IC). Here we describe the molecular analysis of 13 PWS patients and 17 AS patients who have an imprinting defect but no IC deletion. Heteroduplex and partial sequence analysis did not reveal any point mutations of the known IC elements, either. Interestingly, all of these patients represent sporadic cases, and some share the paternal (PWS) or the maternal (AS) 15q11-q13 haplotype with an unaffected sib. In each of five PWS patients informative for the grandparental origin of the incorrectly imprinted chromosome region and four cases described elsewhere, the maternally imprinted paternal chromosome region was inherited from the paternal grandmother. This suggests that the grandmaternal imprint was not erased in the father's germ line. In seven informative AS patients reported here and in three previously reported patients, the paternally imprinted maternal chromosome region was inherited from either the maternal grandfather or the maternal grandmother. The latter finding is not compatible with an imprint-switch failure, but it suggests that a paternal imprint developed either in the maternal germ line or postzygotically. We conclude (1) that the incorrect imprint in non-IC-deletion cases is the result of a spontaneous prezygotic or postzygotic error, (2) that these cases have a low recurrence risk, and (3) that the paternal imprint may be the default imprint.

Angelman Syndrome↗