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Biomedical subjects

I Moore

Publications and source records attributed to I Moore.

At least 19 recordsLinked to original sources
PubMed2006

First precision mass measurements of refractory fission fragments.

Atomic masses of 95-100Sr, 98-105Zr, and [corrected] 102-110Mo and have been measured with a precision of 10 keV employing a Penning trap setup at the IGISOL facility. Masses of 104,105Zr and 109,110Mo are measured for the first time. Our improved results indicate significant deviations from the previously published values deduced from beta end point measurements. The most neutron-rich studied isotopes are found to be significantly less bound (1 MeV) compared to the 2003 atomic mass evaluation. A strong correlation between nuclear deformation and the binding energy is observed in the two-neutron separation energy in all studied isotope chains.

Journal Article↗
PubMed2005

An audit to assess the quality of necropsies performed on stillborn infants.

AIMS: To determine the quality of stillbirth postmortem reports and their contribution to a final diagnosis following the introduction of explicit consent forms after the Alder Hey inquiry. METHODS: Necropsy reports from 100 consecutive stillbirths were reviewed from 2001 onwards. A spreadsheet compiled data items that were considered essential in the Royal College of Pathologists guidelines. The type of consent (with permission for organs/tissue retention) was recorded to assess the impact on establishing a cause of death. RESULTS: Consent for tissue retention was obtained in 95 cases, whereas consent for organ retention was significantly lower (52 cases). In two cases, permission was refused for tissue retention and three requested external examinations only. Of these five, four had an undetermined cause of death, compared with 35 of 95 cases where permission for tissue retention was granted. All data items considered essential were recorded in every report. In 65 cases, the necropsy provided useful information, helped clinical care, and addressed parental concerns. CONCLUSIONS: There was no major impact of the type of necropsy consent on establishing a cause of death, apart from the case of limited necropsies without histological examination of tissue samples.

Autopsy↗
PubMed2001

Case of interstitial 12q deletion in association with Wilms tumor.

A 14-month-old boy presenting with Wilms tumor (WT) was found to have a small de novo deletion of the long arm of chromosome 12 (12q11-12q13.11). Microsatellite analysis of this region from constitutional DNA showed that the paternal allele was absent between the markers D12S331 and D12S1713 (inclusive). In the WT there was no evidence of loss of the maternal chromosome. Constitutional chromosome abnormalities can often point to the presence of genes that are important in disease, and the deletion of chromosome 12 in this patient may indicate a gene involved in WT. To determine whether a WT predisposition locus exists at 12q we examined the region in two familial Wilms tumor (FWT) pedigrees unlinked to the known FWT genes on chromosomes 17q (FWT1), 19q (FWT2), and 11p (WT1). In both families WT did not segregate with chromosome 12q markers located within the deletion boundaries.

Chromosome Deletion↗
PubMed2001

Plant cytokinesis: KNOLLE joins the club.

Dividing plant cells assemble a new intracellular compartment, the cell plate, which grows centrifugally by vesicle fusion to partition the cytoplasm. Genetic studies in Arabidopsis are revealing the molecular signals that specify this special membrane transport pathway.

Arabidopsis↗
PubMed2001

In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib.

Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve these inconsistencies. We investigated in vivo platelet activation in acute thrombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58.3 years) patients with atherothrombotic stroke, and the influence of genotype on markers of platelet activation was assessed. Platelet P-selectin (CD62P) expression and fibrinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sample. Results were compared with matched controls. Neither the 1b allele [allele frequency 0.11 vs. 0.13, odds ratio (OR) confidence interval (CI) 0.8 (0.5-1.3)] nor the 2b allele [0.09 vs. 0.07, OR (CI) 1.4 (0.8-2.4)] was significantly over-represented in patients. Increased numbers of activated platelets were found following stroke (acute mean P-selectin expression 0.64% vs. control 0.35%, P < 0.001; acute mean fibrinogen binding 1.6% vs. control 0.9%, P < 0.001). Activation persisted in the convalescent phase (P < 0.001 and P = 0.005 vs. controls for P-selectin and fibrinogen respectively). Expression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P > 0.95 for each marker, Scheffe's test) or the 2a/2b genotype (P > 0.95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genotypes. These data suggest an underlying prothrombotic state, but do not support the polymorphisms studied as risk factors for thrombotic stroke in this population.

Case-Control Studies↗
PubMed2001

Prevention of fat-induced insulin resistance by salicylate.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may involve fat-induced activation of a serine kinase cascade involving IKK-beta. To test this hypothesis, we first examined insulin action and signaling in awake rats during hyperinsulinemic-euglycemic clamps after a lipid infusion with or without pretreatment with salicylate, a known inhibitor of IKK-beta. Whole-body glucose uptake and metabolism were estimated using [3-(3)H]glucose infusion, and glucose uptake in individual tissues was estimated using [1-(14)C]2-deoxyglucose injection during the clamp. Here we show that lipid infusion decreased insulin-stimulated glucose uptake and activation of IRS-1-associated PI 3-kinase in skeletal muscle but that salicylate pretreatment prevented these lipid-induced effects. To examine the mechanism of salicylate action, we studied the effects of lipid infusion on insulin action and signaling during the clamp in awake mice lacking IKK-beta. Unlike the response in wild-type mice, IKK-beta knockout mice did not exhibit altered skeletal muscle insulin signaling and action following lipid infusion. In summary, high-dose salicylate and inactivation of IKK-beta prevent fat-induced insulin resistance in skeletal muscle by blocking fat-induced defects in insulin signaling and action and represent a potentially novel class of therapeutic agents for type 2 diabetes.

Animals↗
PubMed2000

Technical advance: the DNA-binding activity of gal4 is inhibited by methylation of the gal4 binding site in plant chromatin.

Derivatives of the Saccharomyces cerevisiae transcription factor Gal4 which act as effective transcription activators in yeast, Drosophila, mammalian cells and plant protoplasts are shown to direct expression from a GUS reporter construct when expressed in transgenic tobacco. However, in comparison to 35S-GUS controls, Gal4-mediated expression of the reporter gene was relatively weak and extremely variable. GUS expression was lost as plants matured and it was almost undetectable in most of their progeny. Gal4-mediated gene expression could be restored by treating tissues with 5-aza-cytidine, implicating cytosine methylation in the loss of Gal4-mediated expression. Restoration of reporter expression was not accompanied by an increase in steady-state levels of the activator transcript. We propose that the DNA-binding activity of Gal4 is sensitive to methylation of its binding site in plant chromatin. The Gal4-DNA co-crystal predicts that 5-methylcytosine at either of the outer two positions of the binding site will effectively prevent Gal4 binding. We show that these positions become extensively methylated in transgenic plants and that methylation of Gal4-binding sites interferes with Gal4 binding in vitro. These observations suggest that the Gal4 DNA-binding domain is intrinsically sensitive to cytosine methylation and that, despite the success of Gal4-based expression systems in yeast and Drosophila, Gal4 is not ideal for use in plant gene expression technology.

Azacitidine↗
PubMed2000

A rab1 GTPase is required for transport between the endoplasmic reticulum and golgi apparatus and for normal golgi movement in plants.

We describe a green fluorescent protein (GFP)-based assay for investigating membrane traffic on the secretory pathway in plants. Expression of AtRab1b(N121I), predicted to be a dominant inhibitory mutant of the Arabidopsis Rab GTPase AtRab1b, resulted in accumulation of a secreted GFP marker in an intracellular reticulate compartment reminiscent of the endoplasmic reticulum. This accumulation was alleviated by coexpressing wild-type AtRab1b but not AtRab8c. When a Golgi-targeted and N-glycosylated variant of GFP was coexpressed with AtRab1b(N121I), the variant also accumulated in a reticulate network and an endoglycosidase H-sensitive population appeared. Unexpectedly, expression of AtRab1b(N121I), but not of the wild-type AtRab1b, resulted in a reduction or cessation of vectorial Golgi movement, an effect that was reversed by coexpression of the wild type. We conclude that AtRab1b function is required for transport from the endoplasmic reticulum to the Golgi apparatus and suggest that this process may be coupled to the control of Golgi movement.

Arabidopsis↗
PubMed1998

A transcription activation system for regulated gene expression in transgenic plants.

A widely applicable promoter system is described that allows a gene of interest to be activated in specific plant tissues after a cross between defined transgenic lines. The promoter, pOp, consists of lac operators cloned upstream of a minimal promoter. No expression was detected from this promoter when placed upstream of a beta-glucuronidase (GUS) reporter gene in transgenic plants. Transcription from the promoter was activated by crossing reporter plants with activator lines that expressed a chimeric transcription factor, LhG4. This factor comprised transcription-activation domain-II from Gal4 of Saccharomyces cerevisiae fused to a mutant lac-repressor that binds its operator with increased affinity. When LhG4 was expressed from the CaMV 35S promoter, the spatial and quantitative expression characteristics of the 35S promoter were exhibited by the GUS reporter. The LhG4/pOp system may be used to study toxic or deleterious gene products, to coordinate the expression of multiple gene products, to restrict transgene phenotypes to the F1 generation, and to generate hybrid seed. The LhG4 system offers spatially regulated gene expression in the tissues of whole plants growing under normal conditions without the need for external intervention. It complements inducible expression systems that offer temporal control of gene expression in tissues that can be treated with inducing chemicals.

Bacterial Proteins↗
PubMed1998

Practical implementation of compensators in breast radiotherapy.

BACKGROUND AND PURPOSE: A method of using electronic portal imaging to design compensators for tangential breast irradiation has been developed. We describe how this has been implemented. MATERIALS AND METHODS: The compensator design method generates wedged and unwedged beam weights, in conjunction with templates for multiple lead-sheet compensators and pseudo-CT outlines. The latter describe the breast and lung profiles in a set of transverse slices. The layers of the compensator and pseudo-CT outlines are transferred to a treatment planning system for verification. The accuracy of the planning system for the high transmission blocks used to describe the compensators has been verified using a plotting tank system. Dose volume histogram data and transaxial and sagittal plan slices have been compared for both standard and compensated treatments for a sample set of five patients. RESULTS: The planning system predicted the dose at depths of 1.5 and 5 cm to within 2% for the compensators tested. The biggest source of discrepancy was a consequence of the planning system requiring blocks to have integer percentage transmission. For all patients studied, the compensated treatment resulted in a significant reduction in the percentage volume outside the 95-105% dose, with an average reduction of 10.2%. The percentage volume outside the 95-107% dose was also reduced by typically 3.4%. The implementation was found to yield a convenient automatic method of designing compensators using electronic portal imaging and verifying the results using a planning system. CONCLUSIONS: These results indicate that this method of implementation can be used in practice. The dosimetric accuracy of the treatment planning system is limited by the requirement that blocks should be of integer transmission, but this effect is small.

Breast Neoplasms↗
PubMed1998

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy.

OBJECTIVE: To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia. DESIGN: Review of casenotes by a multidisciplinary focus group. SAMPLE: All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia. MAIN OUTCOME MEASURES: Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate. RESULTS: Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered. CONCLUSIONS: Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.

Autopsy↗
PubMed1997

A homolog of the mammalian GTPase Rab2 is present in Arabidopsis and is expressed predominantly in pollen grains and seedlings.

Vesicle traffic between the endoplasmic reticulum and the Golgi apparatus in mammals requires the small GTP-binding protein Rab2, but Saccharomyces cerevisiae appears not to have a Rab2 homolog. Here it is shown that the higher plant, Arabidopsis thaliana, contains a gene, At-RAB2, whose predicted product shares 79% identity with human Rab2 protein. Transgenic plants containing fusions between beta-glucuronidase and sequences upstream of At-RAB2 demonstrated histochemical staining predominantly in maturing pollen and rapidly growing organs of germinating seedlings. beta-glucuronidase activity in pollen is first detectable at microspore mitosis and increases thereafter. In this respect, the promoter of At-RAB2 behaves like those of class II pollen-specific genes, whose products are often required after germination for pollen tube growth. Seedling germination and pollen tube growth are notable for their unusually high rates of cell wall and membrane biosynthesis. These results are consistent with a role for At-RAB2 in secretory activity.

Amino Acid Sequence↗
PubMed1997

Extending the overlap of three congenital overgrowth syndromes.

We present the case of a male infant, born prematurely (at 33 weeks gestation) with macrosomia, disproportionate macrocephaly, facial dysmorphism, short penis and a small umbilical defect. He had a large ASD and was ventilated from birth for respiratory distress syndrome. He died at 12 hours of age despite neonatal ITU care. Post-mortem examination showed highly lobulated kidneys with nodules of blastema and foci of hamartomatous change in the medulla. Prominence of pancreatic islet cells and expansion of hepatic portal tracts were also noted. His mother has minor cervical spine abnormalities. We discuss the differential diagnosis and the difficulty in confidently assigning a diagnosis to this patient, as considerable overlap is becoming evident between Simpson-Golabi-Behmel syndrome and Perlman syndrome.

Abnormalities, Multiple↗
PubMed1997

Living with Alzheimer's: understanding the family's and patient's perspective.

With aging, the entire person is affected when one component-whether physical, financial, cognitive, or psychosocial-of an older adult's life is impaired. Individuals with Alzheimer's disease (AD) and their families often present with a complicated variety of needs. Current understandings of AD and related problems must include a sensitivity to the emotions and grief experienced by persons living the losses of Alzheimer's. An integrative approach with the perspective of the family and the individual with AD is crucial to the success of the overall care plan.

Alzheimer Disease↗