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Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fission yeast nascent polypeptide-associated complex binds to four-way DNA junctions.

The four-way DNA junction (X-junction) is both a central intermediate of recombination reactions and, in some cases, a controlling element in transcription and the initiation of DNA replication. Many different proteins have been found to bind to X-junctions in a structure-specific manner. In some cases, this ability only reflects the proteins' general predilection for distorted DNAs but in others the interaction is highly specific and usually signifies that the X-junction is the real target for the protein in vivo. Here we identify the Schizosaccharomyces pombe (Sp) nascent polypeptide associated complex (NAC) as a potent binder of X-junction DNA. NAC is highly conserved in eukaryotes and has reported functions in transcription and the targeting of proteins within the cytosol. NAC is composed of alpha and beta subunits. Each SpNAC subunit has the capacity to bind X-junction DNA, but optimal binding depends on a heterodimer of subunits. Competition assays and binding comparisons using a range of different DNA substrates reveal that SpNAC is highly selective for the X-junction structure. By comparative gel electrophoresis we show that the X-junction is held in its open square conformation when bound by SpNAC. Junction binding is inhibited by concentrations of magnesium ions that are sufficient to "stack" the X-junction, suggesting that SpNAC recognises only the open junction structure. Finally, SpNAC can bind to X-junctions that are already bound by a tetramer of the Escherichia coli RuvA protein, indicating that it interacts with only one face of the junction. The possible biological significance of X-junction binding by SpNAC is discussed.

Amino Acid Sequence↗
PubMed2001

Staging and managing lung tumors using F-18 FDG coincidence detection.

PURPOSE: Fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomographic (PET) imaging can be a vital tool in the evaluation and preoperative staging of pulmonary neoplasms. Imaging studies on the gamma camera using coincidence PET (co-PET) were introduced recently into clinical practice. This prospective study assessed the efficacy of co-PET for identifying primary tumors, mediastinal lymph node involvement, the presence of distant spread, the effect on disease staging, and influence on disease management. PATIENTS AND METHODS: Sixty consecutive patients with 61 lung tumors were enrolled in the study (36 men, 24 women; age range, 32-87 years; mean age, 67 years). Histopathologic confirmation was obtained in 58 patients (59 tumors). RESULTS: In assessments of a primary lesion to establish its malignant or benign nature, the sensitivity rate of co-PET was 96% (53 of 55 lesions), the specificity rate was 83% (5 of 6 lesions), and the accuracy rate was 95% (58 of 61 lesions). In the co-PET assessment of lymph node involvement in which histopathologic confirmation was obtained (n = 32), the sensitivity rate was 89% (8 of 9 lesions), the specificity rate was 91% (21 of 23 lesions), and the accuracy rate was 91% (29 of 32 lesions). Previously unknown distant metastases were correctly identified in eight patients, but five false-positive lesions were detected in the brain. Disease staging was correctly altered in 20 patients (33%), and disease management plans were changed in 20 patients (33%) based on the co-PET findings. Unnecessary surgery was obviated in six patients (10%). One patient was given the chance for curative treatment based on the findings of the co-PET study. CONCLUSION: The evaluation of patients with lung neoplasms using F-18 FDG coincidence detection appears to be reliable.

Adult↗
PubMed2001

Federally funded sexually transmitted disease programs and managed care: a review of current and planned partnerships.

BACKGROUND: The Centers for Disease Control and Prevention requested that sexually transmitted disease (STD) programs report their current activities and plans to collaborate with managed care organizations in their 1999 applications for federal funding. GOAL: To review CDC STD program applications for funding to assess the number of activities between STD programs and managed care organizations. METHODS: Narrative data on managed care topics were abstracted from 59 funding applications (50 states, 7 cites or counties, and 2 US territories), using standard qualitative methods. A coding system was applied to categorize each managed care activity into one of nine categories (interrater reliability, 93%). An expert panel ranked activities by complexity, and these scores were used to develop an overall complexity score for each program. RESULTS: All but 9 of the 59 applicants reported managed care organization activities. Altogether, 208 activities were specifically documented, 45% of which were classified as operational in 1999. The most frequently reported activities involved gathering and giving information and promoting STD care through legislation and state Medicaid activities. CONCLUSIONS: Considerable information transfer and policy action between STD programs and managed care organizations are taking place. Further integration of services and policies should be studied and encouraged to promote the effective treatment of STD.

Centers for Disease Control and Prevention, U.S.↗
PubMed2001

Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus but present in columnar-lined Barrett's esophagus.

OBJECTIVES: The presence of a protective adherent mucus gel barrier against gastric reflux in the healthy esophagus is uncertain. The aim was to characterize the surface mucin composition and determine the extent of any adherent mucus gel layer on the normal esophagus, and compare this with that in Barrett's esophagus. METHODS: Isolated surface mucins were characterized by density centrifugation, gel filtration chromatography, and chemical composition. Adherent surface mucus was visualized in situ on unfixed and cryostat sections of mucosa and biopsies using a method that preserves mucus layer thickness. RESULTS: There was a complete absence of adherent mucus gel layers on normal human, pig, and rat esophagi. This was in contrast to the thick adherent mucous layer (median thickness = 100-200 microm) seen on the corresponding gastric mucosa. Small quantities of glycoprotein with a composition characteristic of a secretory mucin were isolated from the pig esophagus surface. The mucin, density range between 1.44 and 1.48 g x ml(-1), contained 80% carbohydrate and was rich in serine, threonine, and proline. The mucin fragmented into smaller glycoprotein units on proteolysis and partially on reduction. Cryostat sections from columnar-lined esophageal biopsies had a substantial adherent surface mucous layer (median thickness = 90 microm, interquartile range = 84-94 microm) staining for neutral mucins (gastric-type epithelium) and acidic mucins (intestinal metaplasia). CONCLUSIONS: A secretory mucin, with an analysis distinct from that of gastric or salivary mucin, is present in very small quantities on the esophageal mucosa and in amounts insufficient to form an adherent gel layer. It is unlikely that mucus has a role in protecting the normal esophagus against reflux. However, an adherent mucous layer was observed over columnar-lined esophagus, and this may protect against reflux.

Animals↗
PubMed2001

A global perspective on statutory Social Security programs for the sick.

Statutory sickness benefit programs have been adopted in 129 countries. Most have an employment-based strategy, social insurance, that restricts coverage to those in paid formal employment. The cash entitlements provided are predominantly earnings-related. Funding comes overwhelmingly from employer and employee contributions, with only a minority of countries providing government subsidies. A comparative-evaluative assessment methodology is used to assess national statutory intentions with respect to statutory social security provision for the sick. The best-designed statutory program is found in Sweden followed closely by France and then Australia, Austria and Germany. Algeria clearly leads the African rankings, as does Peru in Latin America, Iraq in the Middle East, and Nauru in the Pacific Islands. Turkmenistan has the best-designed statutory program in Asia, by a very small margin. In North America, Canada is well ahead of the United States.

Cost of Illness↗
PubMed2000

The NHS plan.

Explore the source record for details and available documents.

Delivery of Health Care↗
PubMed2000

Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells.

Animals↗
PubMed2000

Partial suppression of the fission yeast rqh1(-) phenotype by expression of a bacterial Holliday junction resolvase.

A key stage during homologous recombination is the processing of the Holliday junction, which determines the outcome of the recombination reaction. To dissect the pathways of Holliday junction processing in a eukaryote, we have targeted an Escherichia coli Holliday junction resolvase to the nuclei of fission yeast recombination-deficient mutants and analysed their phenotypes. The resolvase partially complements the UV and hydroxyurea hypersensitivity and associated aberrant mitoses of an rqh1(-) mutant. Rqh1 is a member of the RecQ subfamily of DNA helicases that control recombination particularly during S-phase. Significantly, overexpression of the resolvase in wild-type cells partly mimics the loss of viability, hyper-recombination and 'cut' phenotype of an rqh1(-) mutant. These results indicate that Holliday junctions form in wild-type cells that are normally removed in a non-recombinogenic way, possibly by Rqh1 catalysing their reverse branch migration. We propose that in the absence of Rqh1, replication fork arrest results in the accumulation of Holliday junctions, which can either impede sister chromatid segregation or lead to the formation of recombinants through Holliday junction resolution.

Cell Nucleus↗
PubMed2000

The Holliday junction resolvase SpCCE1 prevents mitochondrial DNA aggregation in Schizosaccharomyces pombe.

SpCCE1 (YDC2) from Schizosaccharomyces pombe is a DNA structure-specific endonuclease that resolves Holliday junctions in vitro. To investigate the in vivo function of SpCCE1 we made an Spcce1:ura4+ insertion mutant strain. This strain is viable and, despite being devoid of the Holliday junction resolvase activity that is readily detected in fractionated extracts from wild-type cells, exhibits normal levels of UV sensitivity and spontaneous or UV-induced mitotic recombination. In accordance with the absence of a nuclear phenotype, we show by fluorescence microscopy that a SpCCE1-GFP fusion localises exclusively to the mitochondria of S. pombe. In Saccharomyces cerevisiae the homologue of SpCCE1, CCE1, is known to function in the mitochondria where its role appears to be to remove recombination junctions and thus facilitate mitochondrial DNA segregation. A similar function can probably be attributed to SpCCE1 in S. pombe, since the majority of mitochondrial DNA from the Spcce1::ura4- strain is in an aggregated form apparently due to extensive interlinking of DNA molecules by recombination junctions. Surprisingly, this marked effect on the conformation of mitochondrial DNA results in little or no effect on proliferation or viability of the Spcce1::ura4+ strain. Possible explanations are discussed.

Cell Compartmentation↗
PubMed2000

Subtractive hybridization--genetic takeaways and the search for meaning.

Gene expression profiling relies on mRNA extraction from defined cell systems, which in the case of pathological processes necessarily results in the use of small quantities of tissues, sometimes as little as a few cells. This obviates the use of many systems of gene expression profiling and is best carried out using cDNA amplified by poly(A) reverse transcription polymerase chain reaction, which is capable of generating material representative of all the expressed genes in samples as small as one cell. Analysis of this material using subtractive hybridization compares the genes expressed at different stages of a biological/pathological process allowing identification of the all the genes upregulated during the process. The identification of the genes present is not dependent on their prior description or on the choice of genes used in a screen and as such the method is ideal for identifying novel genes or unsuspected genes. We have used the method to identify genes involved in normal osteoblastic differentiation and in Paget's disease of bone and it has been widely used to study normal differentiation and pathological processes in a number of systems. The method, its applications and its relationship with the other methods of gene expression profiling are reviewed.

Cell Differentiation↗
PubMed2000

Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development caused by mutations in the gene TCOF1. Its gene product, treacle, consists mainly of a central repeat domain, which shows it to be structurally related to the nucleolar phosphoprotein Nopp140. Treacle remains mostly uncharacterized to date. Herein we show that it, like Nopp140, is a highly phosphorylated nucleolar protein. However, treacle fails to colocalize with Nopp140 to Cajal (coiled) bodies. As in the case of Nopp140, casein kinase 2 appears to be responsible for the unusually high degree of phosphorylation as evidenced by its coimmunoprecipitation with treacle. Based on these and other observations, treacle and Nopp140 exhibit distinct but overlapping functions. The majority of TCOF1 mutations in TCS lead to premature termination codons that could affect the cellular levels of the full-length treacle. We demonstrate however, that the cellular amount of treacle varies less than twofold among a collection of primary fibroblasts and lymphoblasts and regardless of whether the cells were derived from TCS patients or healthy individuals. Therefore, cells of TCS patients possess a mechanism to maintain wild-type levels of full-length treacle from a single allele.

Cell Nucleolus↗
PubMed2000

Conditions for which onset or hospital admission is potentially preventable by timely and effective ambulatory care.

OBJECTIVES: To identify, using a consensus development process, a list of common conditions likely to be ambulatory care sensitive (ACS); i.e. conditions for which practicable improvements in access to timely and effective ambulatory care in the English National Health Service would either reduce the incidence of the condition or avoid substantial proportions of current hospital admissions. METHODS: Three panels of clinicians each reviewed about a third of an initial list of 174 conditions commonly recorded as hospital discharge diagnoses for residents of the North West Thames Region. For each condition, panellists estimated the proportion of cases currently admitted to hospital for which, given timely and effective ambulatory care: onset of disease could have been prevented; admission for existing disease could have been prevented; admission, once indicated, should take place within 48 hours. After an introductory meeting to discuss and clarify the task, panel members completed three rounds of a questionnaire, with postal feedback between each round, and a second meeting to discuss interim results before the final round. Seventeen general practitioners (GPs) and 17 hospital specialists working in the region comprised the panels. RESULTS: The panels considered that for 30 of the 174 conditions at least 70% of admissions to hospital could be avoided, either by prevention of disease onset or timely and effective ambulatory care, though predominantly through the latter. For each of a further 66 conditions, 50-69% of admissions could be prevented. Within-panel agreement between hospital specialists and GPs was generally good, although the GPs tended to give slightly higher scores for avoidability of admissions than the specialists. There was marked convergence of scores in succeeding rounds. CONCLUSIONS: Although a consensus-based list of ACS conditions cannot be definitive, the clear view of the panels was that the scope for avoiding admission through better ambulatory care is very substantial.

Acute Disease↗
PubMed2000

Displacing place-identity: a discursive approach to locating self and other.

Questions of 'who we are' are often intimately related to questions of 'where we are', an idea captured in the environmental psychological concept of place-identity. The value of this concept is that it attends to the located nature of subjectivity, challenging the disembodied notions of identity preferred by social psychologists. The topic of place identity would thus seem to be a productive point around which the sub-disciplines of social and environmental psychology might meet, answering calls for greater disciplinary cross-fertilization. This study contributes to this project by presenting a sympathetic but critical evaluation of research on place-identity. It argues that such research is valuable in that it has established the importance of place for creating and sustaining a sense of self. However, drawing on recent developments in discursive approaches to social psychology, the authors identify several limitations with existing work on place-identity. This critique is then developed through analysis of an ongoing research programme located in the changing landscapes of the new South Africa.

Humans↗
PubMed2000

Revisional surgery for morbid obesity--conversion to the Lap-Band system.

BACKGROUND: The safety and effectiveness of conversion to the Lap-Band system, of patients who had failure of adequate weight loss and/or severe symptoms from prior bariatric procedures has been measured by prospective evaluation of a consecutive group of 50 patients. METHODS: The patients were drawn as a subgroup of 713 patients who had placement of the Lap-Band system between July 1994 and May 2000. The preceding procedures were gastroplasty (35 patients), non-adjustable gastric banding (11), gastric bypass (2) and jejuno-ileal bypass (2). All operations were by open laparotomy. Initial reversal of the initial procedure was performed in 28 patients. M:F ratio was 6%/94%. Inadequate weight was the primary problem in 69%, and symptoms of obstruction were present in 31%. RESULTS: Significant perioperative complications occurred more frequently than after primary placement (17% vs 1.1%). However, late complications were less frequent (2% vs 18%). In particular, there have been no occurrences of prolapse (slippage) of the stomach through the band or erosion of the band into the stomach in this group to date. Weight loss of 47% of excess weight had occurred at 3-year follow-up. This is not significantly different from the 53% EWL in the primary Lap-Band group. All symptoms of obstruction were relieved by the revision, and a number of comorbidities are seen to be markedly improved. CONCLUSIONS: We observe that, when compared to primary Lap-Band placement, revision of failed bariatric procedures to Lap-Band is associated with more perioperative adverse events but fewer late complications. Weight loss is equivalent and is associated with marked improvement in comorbidities and quality of life. The outcomes are better than have been achieved by revision to another form of gastric stapling and should be considered in those patients who have had an unsatisfactory outcome from other bariatric procedures.

Comorbidity↗