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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 19 recordsLinked to original sources

The genomic sequence and analysis of the swine major histocompatibility complex.

We describe the generation and analysis of an integrated sequence map of a 2.4-Mb region of pig chromosome 7, comprising the classical class I region, the extended and classical class II regions, and the class III region of the major histocompatibility complex (MHC), also known as swine leukocyte antigen (SLA) complex. We have identified and manually annotated 151 loci, of which 121 are known genes (predicted to be functional), 18 are pseudogenes, 8 are novel CDS loci, 3 are novel transcripts, and 1 is a putative gene. Nearly all of these loci have homologues in other mammalian genomes but orthologues could be identified with confidence for only 123 genes. The 28 genes (including all the SLA class I genes) for which unambiguous orthology to genes within the human reference MHC could not be established are of particular interest with respect to porcine-specific MHC function and evolution. We have compared the porcine MHC to other mammalian MHC regions and identified the differences between them. In comparison to the human MHC, the main differences include the absence of HLA-A and other class I-like loci, the absence of HLA-DP-like loci, and the separation of the extended and classical class II regions from the rest of the MHC by insertion of the centromere. We show that the centromere insertion has occurred within a cluster of BTNL genes located at the boundary of the class II and III regions, which might have resulted in the loss of an orthologue to human C6orf10 from this region.

Animals↗

Combined surgery and chemoradiation as a treatment for the Buschke-Löwenstein tumour.

BACKGROUND: The Buschke-Löwenstein tumour (BLT) or giant condyloma acuminata is a rare disease which affects the anogenital region. Although histologically benign, it behaves in a malignant fashion, infiltrating the surrounding tissues. The morbidity and mortality from this tumour is high, as is the risk of recurrence following treatment. It lies on the continuum between the benign condylomata acuminata and squamous cell carcinoma. The human papillomavirus is implicated in its aetiology. Treatment is controversial, with topical chemotherapy, radiotherapy, immunotherapy and radical surgery all having been employed. Chemoradiation remains the mainstay of treatment for anal cancers but has not been routinely employed in the management of the BLT without squamous cell carcinoma transformation. METHODS: Two cases of extensive perineal BLT treated with chemoradiation and subsequent surgical excision are presented. RESULTS: The first patient had a good symptomatic response to the chemoradiation but unfortunately died of recurrent disease following surgery. The second patient had a macroscopically complete response to chemoradiation and remains well following abdominoperineal excision. CONCLUSION: Pre-operative chemoradiation has proved to be useful in management for histologically proven benign BLT

Abdominal Neoplasms↗

Interpersonal sensitivities: their links to mood, anger and gender.

This paper explores two interpersonal sensitivities (to rejection and to social put-down) in a group of 54 depressed men and 50 depressed women. Measures of anhedonia, anxiety, anger, social comparison, and submissive behaviour were also obtained. We found no differences in rejection sensitivity, anger, anhedonia, or anxiety between the sample of depressed men and women. Depressed women rated themselves as more submissive and more inferior than depressed men, and blamed themselves more for being criticized and put-down by other people. Principal components analysis (PCA) revealed three underlying factors: mood (including anxiety and depression), internalization (related to self-blame and feelings of low rank), and externalization (related to anger and blaming others for criticism). For both men and women internalization was significantly correlated with depression. However, externalization was negatively related to depression in women, but positively related to depression in men.

Adult↗

Ensembl 2005.

The Ensembl (http://www.ensembl.org/) project provides a comprehensive and integrated source of annotation of large genome sequences. Over the last year the number of genomes available from the Ensembl site has increased by 7 to 16, with the addition of the six vertebrate genomes of chimpanzee, dog, cow, chicken, tetraodon and frog and the insect genome of honeybee. The majority have been annotated automatically using the Ensembl gene build system, showing its flexibility to reliably annotate a wide variety of genomes. With the increased number of vertebrate genomes, the comparative analysis provided to users has been greatly improved, with new website interfaces allowing annotation of different genomes to be directly compared. The Ensembl software system is being increasingly widely reused in different projects showing the benefits of a completely open approach to software development and distribution.

Animals↗

Vibrato of saxophones.

Several alto saxophone players' vibratos have been recorded. The signals are analyzed using time-frequency methods in order to estimate the frequency modulation (vibrato rate) and the amplitude modulation (vibrato extent) of each vibrato sample. Some parameters are derived from the results in order to separate the two ways of vibrato playing: vibrato "à la machoire" and vibrato "sur l'air." Moreover, time domain simulations of single-reed instrument vibratos are created. The model is controlled by two parameters: the mouth overpressure and a parameter characterizing the reed-mouthpiece system. Preliminary comments and comparisons between the simulated vibratos and recorded vibratos results are made.

Acoustics↗

Survey for co-occurrence of ochratoxin A and aflatoxin B1 in dried figs in Turkey by using a single laboratory-validated alkaline extraction method for ochratoxin A.

A survey was carried out to determine the co-occurrence of ochratoxin A and aflatoxin B1 in dried figs from Turkey. Samples from two seasons of crops (2003 and 2004) intended for export to the European Union and the 2004 crop obtained from the domestic Turkish market were analyzed. Affinity column cleanup methods were employed for determining separately ochratoxin A and aflatoxin B1, but for ochratoxin A an alkaline extraction procedure was employed (in contrast to the conventionally employed acidic extraction), which gave consistently higher toxin recovery. In-house validation of the ochratoxin A method gave a limit of detection of 0.15 ng/g and a limit of quantification of 0.5 ng/g with a repeatability of 5.8% in the range 5 to 10 ng/g (with a mean recovery of 94% for spiked samples). Positive results for ochratoxin A were confirmed by liquid chromatography-mass spectrometry. For the 2003 export figs (58 samples), 7 samples contained only aflatoxin B1, 2 samples contained only ochratoxin A, and 2 samples contained both toxins (with maximum concentrations of 35.1 ng/g for aflatoxin B1 and 13.0 ng/g for ochratoxin A). Similarly for the 2004 export figs (41 samples), 16 samples contained only aflatoxin B1, 4 samples contained only ochratoxin A, and 2 samples contained both toxins (with maximum concentrations of 20.6 ng/g for aflatoxin B1 and 26.3 ng/g for ochratoxin A). Of 20 retail samples of dried figs from Turkey, only one sample contained ochratoxin A (2.0 ng/g) and none were contaminated with aflatoxin B1. This survey revealed a 14 to 15% incidence of occurrence of ochratoxin A for 2 years, which is higher than previously reported.

Aflatoxin B1↗

Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease).

Familial idiopathic basal ganglia calcification (IBGC, Fahr disease) is an inherited neurologic condition characterized by basal ganglia and extra-basal ganglia brain calcifications, parkinsonism, and neuropsychiatric symptoms. The authors examined six families for linkage to the previously identified genetic locus (IBGC1) located on chromosome 14q. The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC.

Basal Ganglia Diseases↗

Ensembl 2004.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organize biology around the sequences of large genomes. It is a comprehensive and integrated source of annotation of large genome sequences, available via interactive website, web services or flat files. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. The facilities of the system range from sequence analysis to data storage and visualization and installations exist around the world both in companies and at academic sites. With a total of nine genome sequences available from Ensembl and more genomes to follow, recent developments have focused mainly on closer integration between genomes and external data.

Animals↗

Cattle protected from onchocerciasis by ivermectin are highly susceptible to infection after drug withdrawal.

Ivermectin administration is now the major tool in the control of human onchocerciasis (caused by Onchocerca volvulus) based on its suppression of microfilariae and hence the prevention of disease. However, in Africa, transmission is not eliminated and treated populations continue to be exposed to infective larval (L(3)) challenge, albeit at reduced levels. We have investigated whether protective immunity might develop under such conditions using the analogous host-parasite system Onchocerca ochengi in cattle, based on our previous findings in cattle exposed to challenge, that in vivo ivermectin attenuates the development of adult infections and that irradiation-attenuated L(3) induce significant protection. In a two-phase prospective study over 4 years, groups of cattle were exposed to severe natural challenge. In the first phase, 38/40 animals treated either with ivermectin or with moxidectin at either monthly or 3-monthly intervals had not developed detectable infections after 22 months of exposure whereas, in a non-treated control group (n = 14) nodule prevalence was 78.6% and the geometric mean (range) nodule load was 4.8 (0-33). In the second phase, all drug treatments were withdrawn, a new control group (n = 8) introduced, and exposure continued at the same site. After 24 months, all groups had developed patent infections, with geometric mean (range) nodule loads of 17.4 (4-99), 38.4 (10-111), 50.7 (26-86), 14.3 (0-69) and 14.7 (0-55) for the control, monthly-ivermectin, 3-monthly ivermectin, monthly moxidectin and 3-monthly moxidectin groups, respectively. There was no evidence of protection-indeed the 3-monthly ivermectin group was significantly (P < 0.05) hyper-susceptible. In addition, microfilarial densities and the rate of increase in microfilarial load were significantly higher (P < 0.05) in the ivermectin-treated groups than in control animals. These results have important implications for ivermectin-based control of human onchocerciasis and suggest that humans exposed to ongoing transmission in endemic areas whilst receiving ivermectin are unlikely to develop immunity and will be highly susceptible should drug distribution cease.

Animals↗

Prevalence of hypospadias and other genital anomalies among singleton births, 1988-1997, in Scotland.

BACKGROUND: Considerable debate exists on the epidemiology of genital anomalies. METHODS: All genital anomalies, excluding undescended testes, were identified from neonatal returns, stillbirth and infant death survey records, and returns relating to hospital admissions and linked to form infant profiles on a cohort of singleton births between 1988 and 1997 with follow up for a minimum of three years. FINDINGS: The mean genital anomaly prevalence rate in Scotland was calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9 per 1000 births in 1996. However, there was no evidence of a clear trend to an increasing prevalence of hypospadias, which constituted 73% of the anomalies studied. Logistic regression analysis of the data also showed this rate to be independently associated with being relatively small for gestational age (odds ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05). Infants born in deprived areas, as judged by the Carstairs deprivation score, were least likely to have a genital anomaly (OR 0.73, p < 0.01). INTERPRETATION: A new linked register of congenital genital anomalies in Scotland suggests that over a decade, the birth prevalence of genital anomalies has changed little. The associations between genital anomalies, maternal age, and socioeconomic deprivation require further study.

Cohort Studies↗

Ensembl 2002: accommodating comparative genomics.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of human, mouse and other genome sequences, available as either an interactive web site or as flat files. Ensembl also integrates manually annotated gene structures from external sources where available. As well as being one of the leading sources of genome annotation, Ensembl is an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements. These range from sequence analysis to data storage and visualisation and installations exist around the world in both companies and at academic sites. With both human and mouse genome sequences available and more vertebrate sequences to follow, many of the recent developments in Ensembl have focusing on developing automatic comparative genome analysis and visualisation.

Animals↗

The treatment of de novo acromegalic patients with octreotide-LAR: efficacy, tolerability and cardiovascular effects.

AIM: Somatostatin analogues are normally used as adjunctive therapy to surgery and radiotherapy in management of acromegaly. We studied the effects of de novo OCT-LAR treatment on growth hormone (GH) suppression, tumour size, cardiovascular function, clinical symptoms, signs and quality of life in 9 newly diagnosed acromegalic patients. METHODS: Patients commenced OCT-LAR 20 mg IM monthly for 2 months. Dose increased to 30 mg monthly if mean serum GH (MGH) > 5 mU/l (2 microg/litre) (7 patients). Treatment continued for 6 months. Cardiac function assessed by echocardiography at baseline and day 169. Left ventricular (LV) mass and ejection fraction (EF) calculated from 2D M-mode studies. RESULTS: Serum GH demonstrated suppression in 8/9 patients (mean suppression 64.9% +/- 29.7%, range; 4-95.2%). MGH suppressed < 5 mU/ (2 microg/litre) in 3 (33%) patients. IGF-I and IGFBP3 normalised in 1 (12.5%) and 3 (38%) patients respectively. Tumour shrinkage seen in 30% patients. Eight patients were assessed by echocardiography. At baseline, 7 patients demonstrated abnormalities in LV mass and EF. At day 169, 6 patients demonstrated a fall and 1 an increase in LV mass. Overall there was no significant change in LV mass. A significant increase in EF was observed (p = 0.02). There were significant improvements in health perception (p = 0.01), fatigue (p < 0.05) and perspiration (p = 0.0039). CONCLUSIONS: These data demonstrate OCT-LAR provides adequate control of acromegaly in a proportion of patients treated over 6 months. This is associated with improved LV function, evidenced by increased EF. Improved results are expected with longer-term treatment. OCT-LAR may be considered as primary treatment for acromegaly in selected patients.

Acromegaly↗

The Ensembl genome database project.

The Ensembl (http://www.ensembl.org/) database project provides a bioinformatics framework to organise biology around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of the human genome sequence, with confirmed gene predictions that have been integrated with external data sources, and is available as either an interactive web site or as flat files. It is also an open source software engineering project to develop a portable system able to handle very large genomes and associated requirements from sequence analysis to data storage and visualisation. The Ensembl site is one of the leading sources of human genome sequence annotation and provided much of the analysis for publication by the international human genome project of the draft genome. The Ensembl system is being installed around the world in both companies and academic sites on machines ranging from supercomputers to laptops.

Computational Biology↗

Comparison of Canadian Fusarium graminearum isolates for aggressiveness, vegetative compatibility, and production of ergosterol and mycotoxins.

Fusarium graminearum is the predominant pathogen causing fusarium head blight of cereals in North America. Fifteen Canadian isolates of Fusarium graminearum were highly diverse in terms of vegetative compatibility grouping (VCG) and varied for production of ergosterol and mycotoxin production in rice culture. Aggressiveness was assessed by scoring the disease severity incited in wheat spikes by each isolate. Two inoculation methods, single-floret injection and spray of entire spikes, were used to screen 4 wheat varieties for reaction to the F. graminearum isolates. All isolates were of broadly similar aggressiveness, with disease severity ranging from 17.2 to 39.1 for single floret injection, and 39.1 to 69.0 for spray inoculation. Disease severity, ergosterol production, and mycotoxin development were not correlated. Using nitrate non-utilizing mutants the 15 isolates were grouped into 14 VCGs. Deoxynivalenol (DON) was produced by all isolates in rice culture, at levels between 0.2 and 249 ppm. 15-acetyldeoxynivalenol was produced by 14 of the 15 isolates at levels between 0.4 and 44.6 ppm. These results reveal a high level of diversity for several characteristics among F. graminearum isolates from Canada.

Culture Media↗

The development of clinical guidelines on paracentesis for ascites related to malignancy.

Malignancy-related ascites gives rise to troublesome symptoms and carries a poor prognosis. Abdominal paracentesis is a widely used and effective procedure for symptom relief, but practice with regard to the procedure itself may vary considerably. Evidence obtained in the context of liver disease probably influences practice in malignancy, although the pathophysiology involved is different. Anecdotal evidence suggested a difference in practice between the Exeter and District Hospice and the adjoining hospital, and this was confirmed by a review of case notes. Patients undergoing paracentesis in the hospital were more likely to have prior ultrasound assessment and to be given intravenous fluids, and had longer drainage times and longer inpatient stays. It seemed that some practices were placing unnecessary burdens on patients whose life expectancy was short. A set of clinical guidelines for the procedure was drawn up, based on the limited evidence available and the practice within the hospice. These guidelines emphasise performing ultrasound investigations only in cases of diagnostic uncertainty, allowing up to 5 L of fluid to drain without clamping, leaving drains in for no more than 6 h and giving intravenous fluids only when specifically indicated. These guidelines were introduced on the oncology ward of the adjoining hospital. The impact on practice was assessed by means of a retrospective case note review of all procedures carried out on the ward in the 6 months before and after the guidelines were introduced. The introduction of guidelines resulted in significant reductions in prior ultrasound assessment, mean length of time drains were left in and mean length of inpatient stay for planned procedures. There were no cases of symptomatic hypotension in the postguidelines group.

Adult↗

Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells.

Experimental studies of complete mammalian genes and other genetic domains are impeded by the difficulty of introducing large DNA molecules into cells in culture. Previously we have shown that GST-Z2, a protein that contains three zinc fingers and a proline-rich multimerization domain from the polydactyl zinc finger protein RIP60 fused to glutathione S-transferase (GST), mediates DNA binding and looping in vitro. Atomic force microscopy showed that GST-Z2 is able to condense 130-150 kb bacterial artificial chromosomes (BACs) into protein-DNA complexes containing multiple DNA loops. Condensation of the DNA loops onto the Z2 protein-BAC DNA core complexes with cationic lipid resulted in particles that were readily transferred into multiple cell types in culture. Transfer of total genomic linear DNA containing amplified DHFR genes into DHFR(-) cells by GST-Z2 resulted in a 10-fold higher transformation rate than calcium phosphate co-precipitation. Chinese hamster ovarian cells transfected with a BAC containing the human TP53 gene locus expressed p53, showing native promoter elements are active after GST-Z2-mediated gene transfer. Because DNA condensation by GST-Z2 does not require the introduction of specific recognition sequences into the DNA substrate, condensation by the Z2 domain of RIP60 may be used in conjunction with a variety of other agents to provide a flexible and efficient non-viral platform for the delivery of large genes into mammalian cells.

Animals↗