Search PubMed⌕ Search

Biomedical subjects

K Dawson

Publications and source records attributed to K Dawson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cell cycle-regulated transcription in fission yeast: Cdc10-Res protein interactions during the cell cycle and domains required for regulated transcription.

In Schizosaccharomyces pombe the MBF (DSC1) complex mediates transcriptional activation at Start and is composed of a common subunit called Cdc10 in combination with two alternative DNA-binding partners, Res1 and Res2. It has been suggested that a high-activity MBF complex (at G1/S) is switched to a low-activity complex (in G2) by the incorporation of the negative regulatory subunit Res2. We have analyzed MBF protein-protein interactions and find that both Res proteins are associated with Cdc10 throughout the cell cycle, arguing against this model. Furthermore we demonstrate that Res2 is capable of interacting with a mutant form of Cdc10 that has high transcriptional activity. It has been shown previously that both Res proteins are required for periodic cell cycle-regulated transcription. Therefore a series of Res1-Res2 hybrid molecules was used to determine the domains that are specifically required to regulate periodic transcription. In Res2 the nature of the C-terminal region is critical, and in both Res1 and Res2, a domain overlapping the N-terminal ankyrin repeat and a recently identified activation domain is important for mediating cell cycle-regulated transcription.

Cell Cycle↗
PubMed1999

A human monoclonal antibody encoded by the V4-34 gene segment recognises melanoma-associated ganglioside via CDR3 and FWR1.

A heterohybridoma cell line producing the human monoclonal antibody (MoAb) MDT.1 has been established. The heavy chain of MoAb MDT.1 is encoded by the VH gene segment V4-34 (previously designated VH4-21), and the light chain is encoded by the V kappa 1-L12a gene segment, both in germline configuration. MDT.1 has reactivity against lipid A, double- and single-stranded DNA, red blood cell associated i antigen, and ganglioside antigens. In a panel of tumour cell lines, MDT.1 reacted specifically with melanoma cells and other tumour cells of neuroectodermal origin. Cellular recognition appears to be via tumour-associated ganglioside antigens, and may involve the minimal essential epitope NeuNac alpha 2-->3Gal beta 1-->-4Glc-. Binding to ganglioside antigen is inhibited by the monoclonal anti-idiotypic antibody 9G4. Since the 9G4 idiotope is located in framework region 1 (FWR1) of V4-34-encoded antibodies, this region is likely to be involved, either directly or indirectly, in ganglioside binding. The complementarity-determining region 3 (CDR3) of MDT.1 is arginine rich, with five out of 12 residues being arginine and these residues are candidates for interaction with the negatively charged ganglioside. The ability of MoAb MDT.1 to recognise ganglioside antigens is associated with potentially useful anti-tumour activity.

Amino Acid Sequence↗
PubMed1998

One thousand initiated cycles of in vitro fertilization in women > or = 40 years of age.

OBJECTIVE: To evaluate the results of IVF in women > or = 40 years of age using their own oocytes. DESIGN: Retrospective study. SETTING: Wolfson and Royal Masonic in vitro fertilization units, London, United Kingdom. PATIENT(S): A total of 1,087 IVF cycles were started in women > or = 40 years of age. INTERVENTION(S): Medical records of patient outcomes were reviewed. MAIN OUTCOME MEASURE(S): Clinical pregnancy, miscarriage, and delivery rates. RESULT(S): Of the 1,087 cycles started in 471 women > or = 40 years of age, 842 reached oocyte retrieval (77.5%) and 702 had embryos transferred (64.6%). The pregnancy rate (PR) was significantly lower in women > or = 40 years of age than in a control group of women <40 years of age (11.3% versus 28.2%). It decreased sharply in women >42 years of age, and no women >45 years of age had a child. Women > or = 40 years of age were more likely to miscarry (27% versus 12.7%). When only one embryo was available for transfer, the PR was 3.3%. When >2 embryos were available for transfer, the PR was similar whether 2 or 3 embryos were replaced. No triplet pregnancy occurred. Women > or = 40 years of age achieved a cumulative PR of 30% after three cycles with a cumulative "take home baby" rate of 21%. CONCLUSION(S): In vitro fertilization is a reasonable treatment for women <45 years of age using their own gametes. Those with a "good response" in their first attempt may be encouraged to complete three cycles with an acceptable chance of conception.

Adult↗
PubMed1998

Effect of enteral nutritional products differing in carbohydrate and fat on indices of carbohydrate and lipid metabolism in patients with NIDDM.

Non-insulin dependent diabetes mellitus (NIDDM) is associated with chronic hyperglycemia, which increases the risk of developing microvascular and macrovascular complications. Elevated triglyceride (TG) and VLDL cholesterol levels and low levels of HDL cholesterol have also been frequently reported in NIDDM patients. A diet high in complex carbohydrate and low in fat is typically recommended for management of NIDDM, however, this has recently been challenged by scientific reports of the benefits of dietary intakes high in monounsaturated fat. Thirty-two individuals with NIDDM were randomized to receive either Ensure with Fibre (30% fat) or a high monounsaturated fatty acid product, Glucerna (50% fat). These products were consumed for 28 days at > 80% of daily energy intake. Post-treatment, dietary compliance was verified by a higher plasma TG 18:1 n-9 (p < 0.001) in the Glucerna group and a higher plasma TG 18:2 n-6 (p < 0.001) in the Ensure with Fibre group. The postprandial rise in blood glucose levels, determined by fingerprick samples, was significantly lower (p < 0.01) in the Glucerna group. Trends of clinical interest were greater mean decreases in the Glucerna group compared to the Ensure with Fibre group in: fructosamine, 9.13 umol/L vs 0.14 umol/L; glucose, 1.61 mmol/L vs 0.63 mmol/L; and insulin, 46.0 pmol/L vs 12.6 pmol/L; respectively. However, overall, fasting plasma glucose, fructosamine, TG and cholesterol levels were not significantly different between groups. Thus, in these patients, the high monounsaturated fat diet and the standard diet were similar with regard to usual indicators of carbohydrate and lipid metabolism. A high monounsaturated fat diet appears to pose no risk to lipoprotein metabolism in NIDDM patients.

Adolescent↗
PubMed1996

Naming and knowing in dementia of Alzheimer's type.

We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.

Aged↗
PubMed1996

Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation.

OBJECTIVE: Biliary reconstruction in orthotopic liver transplantation is increasingly being performed without T tube drainage. This increases the difficulty of diagnosing subsequent biliary tract problems, with a greater reliance placed on endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of biliary tract complications. The usefulness of ERCP was evaluated in patients who underwent liver transplant where biliary reconstruction was not done with T tube drainage. DESIGN AND PARTICIPANTS: A retrospective study of the case notes of 90 patients who underwent liver transplantation, and in whom the biliary reconstruction was by end to end choledochocholedochostomy without T tube splintage. RESULTS: ERCP was performed as the primary procedure to investigate a suspected biliary complication in 30 patients (33%). The procedure was successful in 26 patients (87%), and showed a biliary stricture in 12 patients and a bile leak in six patients. ERCP was normal in seven patients and demonstrated dilated ducts alone in one patient. Six of the biliary strictures were successfully dilated endoscopically (50%), but none of the bile leaks resolved with endoscopic drainage. CONCLUSION: This study confirms the diagnostic role of ERCP post liver transplant. The therapeutic role requires clearer evaluation with a controlled trial.

Adolescent↗
PubMed1995

Conditional immortalization of primary cells by human papillomavirus type 18 E6 and EJ-ras defines an E6 activity in G0/G1 phase which can be substituted for mutations in p53.

The human papillomavirus (HPV) type 18 E6 gene cooperates with activated Ha-ras to immortalize primary mouse cells in culture. Using a plasmid where HPV18 E6 expression is regulated by the glucocorticoid inducible MMTV LTR, we have generated immortalized cell lines in which the continued expression of E6 was necessary for maintenance of the transformed phenotype. In the absence of exogenously added hormone these cells were found to arrest in G0/G1. Furthermore, we demonstrate that the effects of E6 were essentially p53 independent and therefore define a novel function by which E6 is able to modulate cell proliferation. In addition, when the E6 dependent cells were maintained under conditions of prolonged growth arrest by the removal of E6, revertant cells were isolated which were no longer dependent on E6 expression for continued proliferation. These revertant cells were found to have acquired a mutation in the cellular gene p53, suggesting that certain p53 mutations are dominant over an E6 requirement in this assay.

Animals↗
PubMed1995

The use of fluorescent in-situ hybridization (FISH) for the analysis of in-vitro fertilization embryos: a diagnostic tool for the infertile couple.

We use triple colour fluorescent in-situ hybridization (FISH) to sex human embryos for preimplantation diagnosis of X-linked disease, to analyse chromosome numbers in embryos donated for research purposes and as a diagnostic tool for patients undergoing infertility treatment, especially in cases where abnormal embryo development occurs. We have reported on the use of FISH in a case where all embryos showed accelerated cleavage. Here we report on the use of triple colour FISH in a case where five out of seven oocytes were multi-nucleated when examined for pronuclei. The embryos were spread whole using HCl/Tween 20 and triple colour FISH performed with probes for chromosomes X, Y and 1 in a 2 h procedure. Two embryos were normal for the probes used, and three showed abnormalities, including one 4-cell embryo where all nuclei were X,X,X,Y,1,1,1,1. FISH indicated that fertilization had occurred, but that the majority of embryos were abnormal confirming that such embryos should not be considered for transfer. In these cases, or where there is recurrent in-vitro fertilization failure or spontaneous abortions, embryos in future cycles can be examined using FISH to ascertain the level of chromosome abnormality which may aid future infertility treatment.

Blastocyst↗
PubMed1995

Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi.

The purpose of the study was to evaluate the interlaboratory agreement of broth dilution susceptibility methods for five species of conidium-forming (size range, 2 to 7 microns) filamentous fungi. The methods used included both macro- and microdilution methods that were adaptations of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (m27-P). The MICs of amphotericin B, fluconazole, itraconazole, miconazole, and ketoconazole were determined in six centers by both macro- and microdilution tests for 25 isolates of Aspergillus flavus, Aspergillus fumigatus, Pseudallescheria boydii, Rhizopus arrhizus, and Sporothrix schenckii. All isolates produced clearly detectable growth within 1 to 4 days at 35 degrees C in the RPMI 1640 medium. Colony counts of 0.4 x 10(6) to 3.3 x 10(6) CFU/ml (mean, 1.4 x 10(6) CFU/ml) were demonstrated in 90% of the 148 inoculum preparations. Overall, good intralaboratory agreement was demonstrated with amphotericin B, fluconazole, and ketoconazole MICs (90 to 97%). The agreement was lower with itraconazole MICs (59 to 79% median). Interlaboratory reproducibility demonstrated similar results: 90 to 100% agreement with amphotericin B, fluconazole, miconazole, and ketoconazole MICs and 59 to 91% with itraconazole MICs. Among the species tested, the MICs for S. schenckii showed the highest variability. The results of the study imply that it may be possible to develop a reference method for antifungal susceptibility testing of filamentous fungi.

Aspergillus↗
PubMed1995

Rational prescribing for acute bronchiolitis.

Acute bronchiolitis is the commonest lower respiratory illness of infancy and early childhood, and it is usually associated with respiratory syncytial virus infection. In the majority of infants, the illness is self-limiting and hence management is directed at maintaining fluid intake, minimal handling and close observation. Children who develop apnoea, fatigue and/or feeding difficulties as well as progressive respiratory distress require hospital admission. Oxygen, intravenous fluids and minimal handling are the pillars of hospital management, and less than 1% of hospitalised infants require additional assisted ventilation. Pharmacological therapy of acute bronchiolitis is contentious. Sympathomimetics are the drugs most frequently used. Inhaled salbutamol (albuterol) has been associated with both positive and negative outcomes. Recent work suggests that nebulised racemic adrenaline (epinephrine) may be helpful in reducing respiratory distress, but further work is needed to confirm this finding. The use of the antiviral drug ribavirin (tribavirin) in acute bronchiolitis remains very contentious. The overwhelming majority of infants do not require the drug and debate remains as to its true effectiveness. The literature tends to support its use in patients with underlying heart or lung disease, but the drug may not be cost effective in this setting. However, the costs of ribavirin therapy could be reduced by the implementation of more rigid treatment guidelines. A reduction in the use of bronchodilators, antibiotics and corticosteroids would help to reduce the overall costs of management. To date, acute bronchiolitis has not lent itself to pharmacological treatment and prescribing should therefore be very strictly audited by clinicians.

Acute Disease↗
PubMed1994

Efficacy and safety of fluvastatin in patients with non-insulin-dependent diabetes mellitus and hyperlipidemia.

The purpose of this study was to investigate the triglyceride-lowering effect of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in the combined hyperlipidemia of non-insulin-dependent diabetes mellitus (NIDDM). In this double-blind trial, 66 patients with NIDDM (24 men and 42 women, age 37-71), with low-density lipoprotein cholesterol (LDL-C) levels of 130-300 mg/dL (3.4-7.8 mmol/L) and triglyceride (TG) levels of 200-1,000 mg/dL (2.3-11.3 mmol/L) despite an 8-week period of diet modification, were randomized to receive either fluvastatin at 20 mg once daily (at night) or placebo for 6 weeks, followed by an increase of fluvastatin to 20 mg twice daily for an additional 6 weeks of treatment. After 12 weeks, fluvastatin decreased plasma levels of total cholesterol by 19.9% (p < 0.001), LDL-C by 24.3% (p < 0.001), TG by 15.3% (p < 0.01), very low-density lipoprotein cholesterol (VLDL-C) by 19.7% (p < 0.001), apolipoprotein (apo) B by 21.3% (p < 0.001), and apo E by 18.1% (p < 0.05), whereas high-density lipoprotein cholesterol (HDL-C) levels were increased by 4.6% (p < 0.05). Within the intermediate-density lipoprotein cholesterol (IDL-C) fraction, a constituent analysis revealed a total cholesterol reduction of 35% (p < 0.01). Greater decreases in TG were seen in patients who had higher levels of TG at baseline. Slight increases in glycemic indices and body weight were seen in both treatment groups. The occurrence of clinical and laboratory abnormalities was similar with both active treatment and placebo, and no myositis was observed. Slight increases in aspartate (ASAT; mean 5.6 U/L at the higher dose) and alanine (ALAT; mean 5.1 U/L at the higher dose) aminotransferases were not clinically significant. In this first, parallel-group placebo-controlled trial of a reductase inhibitor in a free-living NIDDM population, fluvastatin safely improved the combined TG, VLDL-C, IDL-C, LDL-C, and HDL-C abnormalities associated with NIDDM.

Adult↗