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J N Thompson

Publications and source records attributed to J N Thompson.

At least 19 recordsLinked to original sources
PubMed2006

The appearances of oesophageal carcinoma demonstrated on high-resolution, T2-weighted MRI, with histopathological correlation.

This paper describes the spectrum of imaging features of oesophageal adenocarcinoma seen using high-resolution T2-weighted (T2W) magnetic resonance imaging (MRI). Thirty-nine patients with biopsy-proven oesophageal adenocarcinoma were scanned using an external surface coil. A sagittal T2W sequence was used to localise the tumour and to plan axial images perpendicular to the tumour. Fast spin-echo (FSE) T2W axial sequence parameters were: TR/TE, 3,300-5,000 ms/120-80 ms; field of view (FOV) 225 mm, matrix 176x512(reconstructed) mm to 256x224 mm, giving an in-plane resolution of between 1.28x0.44 mm and 0.88x1.00 mm, with 3-mm slice thickness. Thirty-three patients underwent resection and the MR images were compared with the histological whole-mount sections. There were four T1, 12 T2, and 17 T3 tumours. The T2W high-resolution MRI sequences produced detailed images of the oesophageal wall and surrounding structures. Analysis of the imaging appearances for different tumour T stages enabled the development of imaging criteria for local staging of oesophageal cancer using high-resolution MRI. Our study illustrates the spectrum of appearances of oesophageal cancer on T2W high-resolution MRI, and using the criteria established in this study, demonstrates the potential of this technique as an alternative non-invasive method for local staging for oesophageal cancer.

Adenocarcinoma↗
PubMed2005

Deleterious genomic mutation rate for viability in Drosophila melanogaster using concomitant sibling controls.

New deleterious mutations may reduce health and fitness and are involved in the evolution and maintenance of numerous biological processes. Hence, it is important to estimate the deleterious genomic mutation rate (U) in representative higher organisms. However, these estimated rates vary widely, mainly because of inadequate experimental controls. Here we describe an experimental design (the Binscy assay) with concomitant sibling controls and estimate U for viability in Drosophila melanogaster to be 0.31. This estimate, like most published studies, focuses on viability mutations and the overall deleterious genomic mutation rate would therefore be higher.

Animals↗
PubMed2004

Colorectal surgery: the risk and burden of adhesion-related complications.

OBJECTIVES: Adhesions are associated with serious medical complications. This study examines the real-time burden of adhesion-related readmissions following colorectal surgery and assesses the impact of previous surgery on adhesion-related outcomes. PATIENTS AND METHODS: The study used data from the Scottish National Health Service Medical Record Linkage Database to identify three cohorts of patients who had undergone open colorectal surgery during the financial years 1996-97, 1997-98 and 1998-99. Each cohort was followed up for at least 2 years and the number and category of adhesion-related readmissions was recorded. The influence of any previous operations on adhesion-related readmissions was also determined by performing a subanalysis within the 1996-97 cohort of patients who had no record of abdominal surgery within either the previous 5 or 15 years. The relative risk of adhesion-related readmissions was also assessed. RESULTS: In the 1996-97 cohort, 9.0% of patients were readmitted within a year after surgery; 2.1% had complications directly related to adhesions and 6.9% had complications that were possibly related. After 4 years, 19.0% of patients were readmitted for reasons directly or possibly related to adhesions. Many patients were readmitted on more than one occasion and the relative risk of adhesion-related complications was 29.7 per 100 initial procedures over 4 years. In the subgroups that had no record of abdominal surgery within the previous 5 or 15 years, the relative risks of adhesion-related complications were 24.8% and 23.5%, respectively. There was no change in the rate of adhesion-related readmissions following colorectal surgery between 1996 and 1999. CONCLUSION: Colorectal surgery is associated with a considerable rate of adhesion-related readmissions. Preventative measures should be considered to reduce this risk.

Adult↗
PubMed2003

A model of mucopolysaccharidosis IIIB (Sanfilippo syndrome type IIIB): N-acetyl-alpha-D-glucosaminidase deficiency in Schipperke dogs.

Mucopolysaccharidosis III (MPS III) is characterized by lysosomal accumulation of the glycosaminoglycan (GAG) heparan sulphate (HS). In humans, the disease manifests in early childhood, and is characterized by a progressive central neuropathy leading to death in the second decade. This disease has also been described in mice (MPS IIIA and IIIB), dogs (MPS IIIA), emus (MPS IIIB) and goats (MPS IIID). We now report on dogs with naturally occurring MPS IIIB, detailing the clinical signs, diagnosis, histopathology, tissue enzymology and substrate levels. Two 3-year-old Schipperke dogs were evaluated for tremors and episodes of stumbling. Examination of the animals found signs consistent with cerebellar disease including dysmetria, hind limb ataxia and a wide-based stance with truncal swaying. There were mildly dystrophic corneas and small peripheral foci of retinal degeneration. Magnetic resonance imaging of the brain and skeletal radiographs were normal. Intracytoplasmic granules were found in the white cells of peripheral blood and cerebral spinal fluid, and in myeloid lineages in bone marrow. Electrophoresis of urinary GAGs indicated the presence of HS, while assays of cultured fibroblasts found N-acetyl-alpha-D-glucosaminidase (Naglu) activity of between 4.3% and 9.2% of normal. Owing to neurological deterioration, both dogs were euthanized, and post-mortem examinations were performed. Biochemical studies of liver and kidney from both animals demonstrated profound deficiency of Naglu activity and abnormally high GAG levels. Pathology of the brain included severe cerebellar atrophy, Purkinje cell loss, and cytoplasmic vacuolation in neurons and perithelial cells throughout the central nervous system. Pedigree analyses and Naglu levels of family members supported an autosomal recessive mode of inheritance. Using an obligate heterozygote, a breeding colony has been established to aid in understanding the pathogenesis of MPS IIIB and testing of potential therapies.

Acetylglucosaminidase↗
PubMed2003

Coevolution between hosts and parasites with partially overlapping geographic ranges.

Many host species interact with a specific parasite within only a fraction of their geographical range. Where host and parasite overlap geographically, selection may be reciprocal constituting a coevolutionary hot spot. Host evolution, however, may be driven primarily by selection imposed by alternative biotic or abiotic factors that occur outside such hot spots. To evaluate the importance of coevolutionary hot spots for host and parasite evolution, we analyse a spatially explicit genetic model for a host that overlaps with a parasite in only part of its geographical range. Our results show that there is a critical amount of overlap beyond which reciprocal selection leads to a coevolutionary response in the host. This critical amount of overlap depends upon the explicit spatial configuration of hot spots. When the amount of overlap exceeds this first critical level, host-parasite coevolution commonly generates stable allele frequency clines rather than oscillations. It is within this region that one of the primary predictions of the geographic mosaic theory is realized, and local maladaptation is prevalent in both species. Past a further threshold of overlap between the species oscillations do evolve, but allele frequencies in both species are spatially synchronous and local maladaptation is absent in both species. A consequence of such transitions between coevolutionary dynamics is that parasite adaptation is inversely proportional to the fraction of its host's range that it occupies. Hence, as the geographical range of a parasite increases, it becomes increasingly maladapted to the host. This suggests a novel mechanism through which the geographical range of parasites may be limited.

Animals↗
PubMed2003

The role of somatic and germline mutations in aging and a mutation interaction model of aging.

Mutations with a deleterious effect that is expressed after the average reproductive period are not effectively selected against and can accumulate in the germline. A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate. This can have an interactive effect, in that it may increase the rate of somatic mutation during an individual's lifetime. The aging individual therefore becomes increasingly mosaic for somatic mutations, which in turn could potentially contribute to the gradual deterioration of biological processes and influence what we experience as senescence. Interventions that reduce somatic and germ cell mutations should, therefore, reduce the aging process in present and future generations.

Aging↗
PubMed2002

Mutation and premating isolation.

While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

Animals↗
PubMed2001

Plant polyploidy and non-uniform effects on insect herbivores.

Genomic duplication through polyploidy has played a central role in generating the biodiversity of flowering plants. Nonetheless, how polyploidy shapes species interactions or the ecological dynamics of communities remains largely unknown. Here we provide evidence from a 4 year study demonstrating that the evolution of polyploidy has reshaped the interactions between a widespread plant and three species of phytophagous moths. Our results show that polyploidy has produced non-uniform effects, with polyploids less attacked by one insect species, but significantly more attacked by two other species. These results suggest that the evolution of plant polyploidy may not generally confer uniform resistance to multiple species of insect herbivores. In the absence of such a uniform release, the extreme evolutionary success of polyploid plants is probably due to factors other than escape from herbivory. Together, these results suggest that a primary consequence of plant polyploidy may be to shape the ecological structure of plant-insect interactions, thereby providing opportunities for diversification in both plant and insect taxa.

Animals↗
PubMed2001

Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation.

Hurler syndrome is the most severe form of a lysosomal storage disease caused by loss of the enzyme alpha-L-iduronidase (encoded by the IDUA gene), which participates in the degradation of glycosaminoglycans (GAGs) within the lysosome. In some populations, premature stop mutations represent roughly two-thirds of the mutations that cause Hurler syndrome. In this study we investigated whether the aminoglycoside gentamicin can suppress stop mutations within the IDUA gene. We found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Determination of alpha-L-iduronidase protein levels by an immunoquantification assay indicated that gentamicin treatment produced a similar increase in alpha-L-iduronidase protein in Hurler cells. Both the alpha-L-iduronidase activity and protein level resulting from this treatment have previously been correlated with mild Hurler phenotypes. Although Hurler fibroblasts contain a much higher level of GAGs than normal, we found that gentamicin treatment reduced GAG accumulation in Hurler cells to a normal level. We also found that a reduced GAG level could be sustained for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation. Taken together, these results suggest that the suppression of premature stop mutations may provide an effective treatment for Hurler syndrome patients with premature stop mutations in the IDUA gene.

Anti-Bacterial Agents↗
PubMed2001

Postoperative adhesions: ten-year follow-up of 12,584 patients undergoing lower abdominal surgery.

PURPOSE: Postoperative adhesions are a significant problem after colorectal surgery. However, the basic epidemiology and clinical burden are unknown. The Surgical and Clinical Adhesions Research Study has investigated the scale of the problem in a population of 5 million. METHODS: Validated data from the Scottish National Health Service Medical Record Linkage Database were used to define a cohort of 12,584 patients undergoing open lower abdominal surgery in 1986. Readmissions for potential adhesion-related disease in the subsequent ten years were analyzed. The methodology was conservative in interpreting adhesion-related disease. RESULTS: In the study cohort 32.6 percent of patients were readmitted a mean of 2.2 times in the subsequent ten years for a potential adhesion-related problem. Although 25.4 percent of readmissions were in the first postoperative year, they continued steadily throughout the study period. After open lower abdominal surgery 7.3 percent (643) of readmissions (8,861) were directly related to adhesions. This varied according to operation site: colon (7.1 percent), rectum (8.8 percent), and small intestine (7.6 percent). The readmission rate was assessed to provide an indicator of relative risk of adhesion-related problems after initial surgery. The overall average rate of readmissions was 70.4 per 100 initial operations, with 5.1 directly related to adhesions. This rose to 116.4 and 116.5, respectively, after colonic or rectal surgery-with 8.2 and 10.3 directly related to adhesions. CONCLUSIONS: There is a high relative risk of adhesion-related problems after open lower abdominal surgery and a correspondingly high workload associated with these readmissions. This is influenced by the initial site of surgery, colon and rectum having both the greatest impact on workload and highest relative risk of directly adhesion-related problems. The study provides sound justification for improved adhesion prevention strategies.

Abdomen↗
PubMed2001

Enhancing the clinical research pipeline: training approaches for a new century.

There is growing concern that the numbers of physician-scientists being trained in U.S. academic health centers will not be sufficient to continue the rate of current progress in biomedical research. The authors believe that the needs of current trainees and junior faculty must be addressed immediately, and that programs to train the next generation of patient-oriented researchers must be established without delay. The authors describe a two-pronged approach to this looming crisis. First is a description of innovative educational programs implemented at one academic health center from the K-12 level through the medical-school curriculum. Second, programs are discussed that have been developed to facilitate the recruitment, training, and retention of physician-scientists in the early parts of their professional careers. Four models of training "translational" investigators are presented, along with case studies of how these models have been implemented in real-life productive and professionally satisfying collaborations within one academic health center. The authors conclude by stating that to be prepared for the effects of future knowledge on human disease and preventive health, academic health centers must enhance training opportunities for physician-scientists.

Humans↗
PubMed2000

Spatial differences in patterns of modification: selection on hairy in Drosophila melanogaster wings.

Artificial selection was carried out for over 45 generations to enhance and suppress expression of the mutation hairy on the Drosophila melanogaster wing. Whole chromosome mapping of X-linked and autosomal modifiers of sense organ number displayed regional differences in magnitude and direction of their effects. Regional specificity of modifier effects was also seen in some interchromosomal interactions. Scanning electron microscopy allowed precise measurement of sense organ size and position along the L3 longitudinal wing vein. Sense organ size varied in a predictable fashion along the proximal-distal axis, and the dorsal pattern differed from the ventral pattern. The high and low selection lines differed most in the proximal portion of the L3 vein. Extra sense organs in the High line were often associated with vein fragments at locations predicted from ancestral vein patterns. Thus, regional specificity of polygenic or quantitative trait locus modifier effects was identified in several different parts of the wing.

Animals↗
PubMed2000

Unrelated umbilical cord blood transplantation in infancy for mucopolysaccharidosis type IIB (Hunter syndrome) complicated by autoimmune hemolytic anemia.

This report describes unrelated umbilical cord blood transplantation for a 10-month-old infant boy with mucopolysaccharidosis IIB (Hunter syndrome), an X-linked metabolic storage disorder due to deficiency of iduronate sulfatase. Two years after transplant approximately 55% normal plasma enzyme activity has been restored and abnormal urinary excretion of glycosaminoglycans has nearly completely resolved. The boy has exhibited normal growth and development after transplant. Nine months after transplant he developed severe autoimmune hemolytic anemia and required 14 months of corticosteroid treatment to prevent clinically significant anemia. Bone marrow transplantation for Hunter syndrome and post-transplant hemolytic anemia are reviewed. Bone Marrow Transplantation (2000).

Adrenal Cortex Hormones↗
PubMed2000

Hazardous materials events: an industrial comparison.

Identifying industries at high risk for hazardous materials releases can facilitate prevention and preparation for such events. A retrospective review by Standard Industrial Classification (SIC) codes was conducted on non-petroleum hazardous materials emergency events from 1993 to 1995 and collected by the Washington State Department of Health in a program supported by the Agency for Toxic Substances and Disease Registry. Annual US Census data were used to determine the number of facilities and employees by SIC code in the state of Washington. SIC codes with the most total events and events per 10,000 employees were ranked and characterized by type of releases. In 3 years, 1269 events were recorded, with 294 involving human victims. Industries with the highest average annual number of events per 10,000 employees were agricultural chemical manufacturing (142); petroleum refining (122); industrial and miscellaneous chemical manufacturing (56); electric light and power (54); and pulp, paper, and paperboard mills (39). Industries with high rates of hazardous materials emergency events should continue to develop methods of preventing these releases.

Emergencies↗
PubMed2000

Use of a questionnaire to improve occupational and environmental history taking in primary care physicians.

New patient charts were reviewed before and after the introduction of a self-administered questionnaire, designed to elicit occupational and environmental (OE) information from patients. The Occupational Health Risk Assessment questionnaire (OHRA) was expected to prompt primary care physicians to make further inquiries into OE health issues. Chart reviews determined the amount and type of information detailed in the primary care physicians' notes. Twenty-three percent of completed OHRAs indicated a job-related health problem. Despite a high prevalence of self-reported work-related symptoms and exposures, the mean number of notations regarding OE exposures was less than one item per patient chart. A comparison of mean OE notations per chart before versus after introduction of the OHRA indicated a decline in notations after introduction of the OHRA (1.03 vs 0.72, P = 0.02). We detail the type of OE issues that patients presented to a primary care practice and the resulting information contained in primary care providers' notes. Suggestions are made to improve a self-administered patient questionnaire to better diagnose, prioritize, and formulate treatment plans related to OE issues.

Adult↗
PubMed2000

Coevolutionary clines across selection mosaics.

Much of the dynamics of coevolution may be driven by the interplay between geographic variation in reciprocal selection (selection mosaics) and the homogenizing action of gene flow. We develop a genetic model of geographically structured coevolution in which gene flow links coevolving communities that may differ in both the direction and magnitude of reciprocal selection. The results show that geographically structured coevolution may lead to allele-frequency clines within both interacting species when fitnesses are spatially uniform or spatially heterogeneous. Furthermore, the results show that the behavior and shape of clines differ dramatically among different types of coevolutionary interaction. Antagonistic interactions produce dynamic clines that change shape rapidly through time, producing shifting patterns of local adaptation and maladaptation. Unlike antagonistic interactions, mutualisms generate stable equilibrium patterns that lead to fixed spatial patterns of adaptation. Interactions that vary between mutualism and antagonism produce both equilibrium and dynamic clines. Furthermore, the results demonstrate that these interactions may allow mutualisms to persist throughout the geographic range of an interaction, despite pockets of locally antagonistic selection. In all cases, the coevolved spatial patterns of allele frequencies are sensitive to the relative contributions of gene flow, selection, and overall habitat size, indicating that the appropriate scale for studies of geographically structured coevolution depends on the relative contributions of each of these factors.

Alleles↗