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D Lane

Publications and source records attributed to D Lane.

At least 19 recordsLinked to original sources
PubMed2006

The p53 knowledgebase: an integrated information resource for p53 research.

The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in the tumor suppressor gene tp53, which affects the key transcriptional regulatory processes in cell growth and death, occur frequently in cancer and helps explain why p53 has been called the guardian of the genome. There is a vast body of published knowledge on all aspects of p53's role in cancer. To facilitate research, it would be helpful if this information could be collected, curated and updated in a format that is easily accessible to the user community. To this end, we initiated the p53 knowledgebase project (http://p53.bii.a-star.edu.sg). The p53 knowledgebase is a user-friendly web portal incorporating visualization and analysis tools that integrates information from the published literature with other manually curated information to facilitate knowledge discovery. This includes curated information on sequence, structural, mutation, polymorphisms, protein-protein interactions, transcription factors, transcriptional targets, antibodies and post-translational modifications that involve p53. The goal is to collect and maintain all relevant data on p53 and present it in an easily accessible format that will be useful to researchers in the field.

Genes, p53↗
PubMed2006

Anaesthetic implications of vascular type Ehlers-Danlos syndrome.

Vascular type Ehlers-Danlos syndrome is an inherited connective tissue disease, which is typified by tissue fragility, joint hypermobility, a tendency to bleed excessively and rupture of the uterus, the bowel and arteries. Two case reports are presented which describe the anaesthetic management of patients with spontaneous bowel perforations due to vascular type Ehlers-Danlos syndrome. Both cases were associated with relatively minor problems. The implications of this condition for anaesthesia include difficulty (and risk of complications) with vascular access, a risk of spontaneous arterial rupture in the perioperative period, possible cervical spine instability and airway trauma on intubation. There is also a risk of excessive bleeding, potentially difficult neuraxial anaesthesia and an increased risk of epidural haematoma. There also may be associated cardiac or pulmonary disease. However, these two cases and the limited previously published literature suggest that such potential complications are actually rare and that anaesthesia may be conducted in a relatively standard manner in most circumstances.

Adult↗
PubMed2005

Novel molecular basis of an Inab phenotype.

The Cromer blood group system consists of ten high-prevalence and three low-prevalence antigens carried on decay-accelerating factor (DAF). DAF is found in the cell membranes of RBCs, granulocytes, platelets, and lymphocytes and is widely represented in other body tissues. Sequence analyses of DNA were performed on a blood sample from a 91-year-old Japanese woman whose serum contained an alloantibody to a high-prevalence antigen in the Cromer blood group system (anti-IFC). A blood sample from her daughter was also studied. Sequence analysis revealed a substitution of 508C7>T in exon 4 of DAF in the proband. The proband's daughter was heterozygous for 508C/T. This study describes an Inab phenotype in which the 508C>T nonsense mutation is predicted to change arginine at amino acid residue 136 to a stop codon. This change is in SCR 3 of DAF. This study reports on the molecular basis of a new proband with the Inab phenotype who had no history of intestinal disorders.

Aged↗
PubMed2003

Improving cancer therapy by non-genotoxic activation of p53.

Inactivation of p53 function is a common event in cancer. Approximately 50% of human tumours express mutant p53 and there is evidence that in others, including many childhood tumours, p53 function is impaired in other ways. These defects in p53 function may be due to the alteration of cellular factors that modulate p53 or to the expression of viral oncoproteins. Radiotherapy and many of the chemotherapeutic drugs currently used in cancer treatment are potent activators of p53. However, most of these therapies have a serious drawback, and that is the long-term consequences of their DNA damaging effects. Here, we review the discoveries in p53 research that are most significant to the development of new therapies based on the induction of the transcriptional activity of p53 in a non-genotoxic way and discuss the situations in which this type of approach may be most beneficial.

Gene Expression Regulation, Neoplastic↗
PubMed2003

Delivery of herpes simplex thymidine kinase bystander effect by engineered human mesothelial cells for the treatment of ovarian cancer.

BACKGROUND: Resistance to conventional chemotherapy is a major clinical problem for ovarian cancer, and long-term survival for patients with advanced-stage disease is rare. Other therapeutic strategies, such as gene therapy, have been explored but several limitations exist, which include low viral vector transduction efficiency, host immune response to the vector, and vector toxicity. METHODS: We developed a cell-based therapy that exploits human mesothelial cells to deliver anticancer modalities for treatment of ovarian cancer. As a proof of concept, we genetically engineered mesothelial with the herpes simplex virus thymidine kinase/ganciclovir (HSVTK/GCV) system to deliver cytotoxicity to human ovarian cancer cells. This system is well characterized, and has been widely used in different gene-therapy based strategies. RESULTS: Our results demonstrate that HSVTK-modified mesothelial cells are sensitive to GCV killing in vitro and support the HSVTK bystander effect. Engineered mesothelial cells can deliver the HSVTK bystander effect to human ovarian cancer cell-lines, as well as to primary ovarian cancer cells. A significant reduction of tumor growth and prolongation of survival in s.c. and i.p. xenograft mouse models of ovarian cancer are obtained with as little as 1% of HSVTK-expressing mesothelial cells. Intraperitoneal administration of HSVTK-expressing mesothelial cells in an established mouse model of ovarian cancer results in a statistically significant prolonged survival of treated animals. Importantly, distribution studies showed that mesothelial cells localize preferentially to tumor sites. DISCUSSION: Our study demonstrates the feasibility of using a mesothelial cell-based therapy for treatment of ovarian cancer, and suggests that this strategy should be further explored.

Adenoviridae↗
PubMed2002

Ethnic differences in blood pressure and the prevalence of hypertension in England.

The objective of this study was to examine the prevalence of hypertension and mean blood pressures among Afro-Caribbeans and South-Asians in England compared with Caucasians. Data from the Birmingham Factory Screen, Birmingham INTERSALT volunteers, and four West Midlands churches were combined into a single database (n = 2853), since all three studies employed identical methods. The cohort comprised 2169 (76%) Caucasians (71% men); 453 (16%) Afro-Caribbean (60% men); and 231 (8%) South-Asian men. The results were that overall prevalence of hypertension (> or =160/95 mm Hg or taking antihypertensives) was greater in both Afro-Caribbean men (31%) and women (34%) (both P < 0.001), compared with Caucasians (19% and 13% respectively), while South-Asian men had a similar overall prevalence to Caucasians (16%). Compared with Caucasians, Afro-Caribbeans had significantly higher mean systolic blood pressure, with higher mean diastolic blood pressures evident among Afro-Caribbean women. After adjustment for age, body mass index, smoking, and weekly alcohol intake, the odds ratios (95% CI) for being hypertensive were 1.56 (1.14 to 2.13; P = 0.005) and 2.40 (1.51 to 3.81; P = 0.0002) for Afro-Caribbean men and women, respectively and 1.31 (0.88 to 1.97; P = 0.19) for South-Asian men, compared with Caucasians. In conclusion the prevalence of hypertension and mean blood pressures are higher among Afro-Caribbeans compared with Caucasians. South-Asian men had similar rates of hypertension and mean blood pressures to Caucasians.

Adult↗
PubMed2001

Role of the ATP-binding site of SopA protein in partition of the F plasmid.

SopA belongs to a large family of bacterial partition protein ATPases. It helps stabilize the F plasmid by acting as the primary repressor of transcription of the sopAB operon, preventing the destabilizing effects of Sop protein excess. It is also thought to act directly in the F partition mechanism. We have examined the role of SopA in partition and repression by observing the consequences of replacing an invariant ATP-binding site lysine, K120, by glutamine or arginine. Circular dichroism studies of the purified mutant proteins revealed no major differences from wild-type, but in the presence of ADP or ATP each protein showed a characteristic spectrum which suggested a distinct conformational change. The K120Q mutant retained most of the wild-type ATPase activity while the K120R mutant lost it. In neither case was the residual activity stimulated by SopB, as occurs for wild-type SopA. The strength of sop promoter repression by the mutant SopA proteins alone was comparable to that resulting from SopB-enhancement of wild-type SopA, but SopB enhanced repression by the mutant SopA proteins either slightly (K120R) or not at all (K120Q). Mini-Fs in which the sop operon was controlled by a constitutive promoter were destabilized by the mutations, demonstrating the need for SopA and its ATP-binding site in the partition process. The K120R mini-F was lost at the same rate as a mini-F lacking the sopC centromere, the K120Q mutant was lost faster. SopAK120R at high levels was more effective than SopA(+) in disrupting the partition complex, whereas SopAK120Q did not disrupt it at all. These results suggest that one function of SopA in the partition mechanism is to break the paired plasmid structure to allow F molecules to segregate to daughter cells.

Adenosine Diphosphate↗
PubMed2001

Delya's story: from expert to novice, a critique of Benner's concept of context in the development of expert nursing practice.

The concepts identified within Benner's Nineteen Eighty Four research 'From Novice to Expert' have been widely adopted within UK nursing education and development. This paper combines a narrative from a post-registration student with analysis of the literature as a case study for gaining greater understanding of Benner's work in practice. Delya's story both validates aspects of the concept of skill acquisition and challenges some of the interpretations of the model within professional education. The focus of the critique of Benner's work within the literature to date has been on a deconstruction of the concepts and semantics of her work. In presenting verbatim extracts from a case study this paper seeks to move the focus to nursing practice.

Decision Making↗
PubMed2001

Predictors of attendance at cardiac rehabilitation after myocardial infarction.

OBJECTIVE: The purpose of this study was to determine predictors of attendance at cardiac rehabilitation after myocardial infarction (MI). METHODS: Various demographic, behavioural, and clinical variables were measured during hospitalisation in 288 MI patients. Of these, 263 were available to attend outpatient-based cardiac rehabilitation: 108 actually attended. RESULTS: Multiple logistic regression analyses indicated that nonattenders lived in more deprived areas and were less likely to have paid employment. Nonattenders also registered more symptoms of depression and anxiety and exercised less frequently prior to their MI, although only the last of these variables were predicted in a multivariate model. In terms of clinical status, whether patients had been thrombolysed or not was the strongest predictor of attendance. CONCLUSIONS: Attendance at cardiac rehabilitation is not an arbitrary matter. Strategies should be developed for encouraging greater attendance among those not in paid employment, those from deprived areas, and those who exercise infrequently.

Aged↗
PubMed2001

Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany.

In a randomized phase II trial in Germany, we investigated the clinical and economic impact of amifostine protection against the hematological and oral toxicities of carboplatin administered concurrently with standard fractions of radiotherapy. 28 patients with squamous cell carcinomas of the head and neck received adjunctive or primary radiotherapy (5 days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy) in conjunction with carboplatin (70 mg/m2) on days 1-5 and days 21-26. All patients received radiation encompassing at least 75% of the major salivary glands. Patients were randomized to receive radiation and carboplatin (RCT) alone or RCT preceded by rapid infusion of amifostine (500 mg) on days carboplatin was administered. The 14 patients who received amifostine, in comparison to 14 patients in the control arm, had significantly fewer episodes of grade 3 or 4 thrombocytopenia (p = 0.001), mucositis (p = 0.001), and xerostomia (p = 0.001). The patients receiving amifostine accrued significantly lower supportive care costs for resources related to infection ($241 vs. $1,275, p < 0.01), red blood cell and platelet support ($286 vs. $1,276 p = 0.06) alimentation ($343 vs. $894, p = .01), and hospitalization ($286 vs. $2,429, p < 0.01). Overall, including the costs of amifostine, mean per patient supportive care costs were $4,401 for the amifostine group and $5,873 (p = .02) for the control group. Our results from a randomized phase II trial indicate that selective cytoprotection with amifostine potentially offers clinical and economic benefits in patients with advanced head and neck cancer receiving radiochemotherapy. Additional economic studies alongside randomized phase III trials and from other countries are needed.

Amifostine↗
PubMed2001

Elution characteristics of tobramycin from polycaprolactone in a rabbit model.

This study investigated the elution characteristics of tobramycin from polycaprolactone, a bioabsorbable polymer, in a rabbit model. Sixty rabbits were divided into two groups. Group 1 had polycaprolactone rods impregnated with 6% tobramycin surgically implanted into the proximal femoral intramedullary canal. Group 2 received polymethylmethacrylate rods of like size, shape, and antibiotic concentration. Serum and urine samples were obtained, and tobramycin levels were determined via fluorescent immunosorbent assay. Rabbits were sacrificed as long as 56 days after surgery. Local bone tobramycin concentration was determined using the agar diffusion method. Polycaprolactone delivered a significantly higher peak bone concentration of tobramycin (22.4 microg/mL) than did polymethylmethacrylate (13.59 microg/mL). Polycaprolactone also had a more gradual decrease in local tobramycin concentration than did polymethylmethacrylate. Neither polycaprolactone nor polymethylmethacrylate yielded consistently detectable (> 0.1 microg/mL) serum tobramycin levels. Urine concentrations mirrored those seen in bone, with polycaprolactone achieving significantly higher tobramycin concentrations than did polymethylmethacrylate. Polycaprolactone had superior elution characteristics compared with polymethylmethacrylate in this lapine model, suggesting that polycaprolactone might be a promising local antibiotic delivery vehicle for the treatment of osteomyelitis.

Animals↗
PubMed2001

Coherent probability from incoherent judgment.

People often have knowledge about the chances of events but are unable to express their knowledge in the form of coherent probabilities. This study proposed to correct incoherent judgment via an optimization procedure that seeks the (coherent) probability distribution nearest to a judge's estimates of chance. This method was applied to the chances of simple and complex meteorological events, as estimated by college undergraduates. No judge responded coherently, but the optimization method found close (coherent) approximations to their estimates. Moreover, the approximations were reliably more accurate than the original estimates, as measured by the quadratic scoring rule. Methods for correcting incoherence facilitate the analysis of expected utility and allow human judgment to be more easily exploited in the construction of expert systems.

Adult↗