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Biomedical subjects

A Parker

Publications and source records attributed to A Parker.

At least 55 records · Page 3Linked to original sources

The development of a self-directed and peer-based clinical training programme.

A reflective learning approach for clinical training with final year students is described. The training programme aims to promote the development of independent and reflective practitioners. The theories and ideas that have influenced the structure of the programme are described and an outline of the programme is provided. The views of students who have participated in the process are discussed. Most students were positive about their experiences, but some problems were reported. Suggestions for improving the supervisory process are considered.

Consumer Behavior↗

Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair.

The human MutY homolog (hMYH) is a DNA glycosylase involved in the removal of adenines or 2-hydroxyadenines misincorporated with template guanines or 7,8-dihydro-8-oxodeoxyguanines. hMYH is associated in vivo with apurinic/apyrimidinic endonuclease (APE1), proliferating cell nuclear antigen (PCNA), and replication protein A (RPA) in HeLa nuclear extracts as shown by immunoprecipitation and Western blotting. However, binding of hMYH to DNA polymerases beta and delta was not detected. By using constructs containing different portions of hMYH fused to glutathione S-transferase, we have demonstrated that the APE1-binding site is at a region around amino acid residue 300, that the PCNA binding activity is located at the C terminus, and that RPA binds to the N terminus of hMYH. A peptide consisting of residues 505-527 of hMYH that contains a conserved PCNA-binding motif binds PCNA, and subsequent amino acid substitution identified Phe-518 and Phe-519 as essential residues required for PCNA binding. RPA binds to a peptide that consists of residues 6-32 of hMYH and contains a conserved RPA-binding motif. The PCNA- and RPA-binding sites of hMYH are further confirmed by peptide and antibody titration. These results suggest that hMYH repair is a long patch base excision repair pathway.

Amino Acid Motifs↗

The effect of cigarette smoking and smoking cessation on spinal fusion.

STUDY DESIGN: The effect of cigarette smoking and smoking cessation on spinal fusion was studied in a retrospective review of 357 patients who had undergone instrumented spinal fusion. OBJECTIVE: To document the widely assumed but unreported benefit of cigarette smoking cessation on fusion rate and clinical outcome after spinal fusion surgery. BACKGROUND DATA: Cigarette smoking has been shown to inhibit lumbar spinal fusion and to adversely effect outcome in treatment of lumbar spinal disorders. Prior reports have compared smokers and nonsmokers, as opposed to comparing smokers and quitters. METHODS: This study retrospectively identified 357 patients who underwent a posterior instrumented fusion at either L4-L5 or L4-S1 between 1992 and 1996. Analysis of the medical record and follow-up telephone surveys were conducted. Clinical outcome and fusion status was analyzed in relation to preoperative and postoperative smoking parameters. RESULTS: In this study, the nonunion rate was 14.2% for nonsmokers and 26.5% for patients who continued to smoke after surgery (P < 0.05). Patients who quit smoking after surgery for longer than 6 months had a nonunion rate of 17.1%. The nonunion rate was not significantly affected by either the quantity that a patient smoked before surgery or the duration of preoperative smoking abatement. Return-to-work was achieved in 71% of nonsmokers, 53% of nonquitters, and 75% of patients who quit smoking for more than 6 months after surgery. DISCUSSION: These results validate the hypothetical assumption that postoperative smoking cessation helps to reverse the impact of cigarette smoking on outcome after spinal fusion.

Adult↗

Self-report of smoking, obesity and hypertension history and survival among a cohort of iowa renal cell carcinoma cases.

PURPOSE: Smoking, obesity and hypertension are well-established risk factors for the development of renal cell carcinoma (RCC). However, little is known regarding the ability of RCC patient history regarding these characteristics to predict future survival.METHODS: To evaluate this question, we conducted follow-up on a cohort of incident RCC cases first assembled in Iowa from 1986-1989 for case-control analysis. We report data on 364 cases aged 40-86 years who reported detailed anthropometric and lifestyle history on a mailed questionnaire. Mortality experiences through 1998 were determined by linkage to the Iowa Cancer Registry and other databases; 233 deaths were identified during the 2,470 total years of follow-up, with 145 of those having RCC listed as the underlying cause of death on the death certificate. The Cox Proportional Hazards model was used to estimate the risk associated with each potential prognostic characteristic.RESULTS: After adjustment for age, a suggestion of an association with survival was noted for history of hypertension [Relative Risk (RR) = 0.8; 95% Confidence Interval (CI) 0.5-1.1] but no association was noted for either smoking or weight history. After further adjustment for tumor stage at diagnosis, evidence of an association for either smoking or obesity remained absent. However, after similar adjustment, the protective effect of history of hypertension actually strengthened slightly (RR = 0.7; CI 0.5-0.9).CONCLUSIONS: Data from this follow-up study of incident RCC cases in Iowa suggests that after adjustment for the strongest independent predictor of survival, a reported history of hypertension is associated with better survival.

Journal Article↗

Purification and characterization of a mammalian homolog of Escherichia coli MutY mismatch repair protein from calf liver mitochondria.

A protein homologous to the Escherichia coli MutY glycosylase, referred to as mtMYH, has been purified from calf liver mitochondria. SDS-polyacrylamide gel electrophoresis, western blot analysis as well as gel filtration chromatography predicted the molecular mass of the purified calf mtMYH to be 35-40 kDa. Gel mobility shift analysis showed that the purified mtMYH formed specific binding complexes with A/8-oxoG, G/8-oxoG and T/8-oxoG, weakly with C/8-oxoG, but not with A/G and A/C mismatches. The purified mtMYH exhibited DNA glycosylase activity removing adenine mispaired with G, C or 8-oxoG and weakly removing guanine mispaired with 8-oxoG. The mtMYH glycosylase activity was insensitive to high concentrations of NaCl and EDTA. The purified mtMYH cross-reacted with antibodies against both intact MutY and a peptide of human MutY homolog (hMYH). DNA glycosylase activity of mtMYH was inhibited by anti-MutY antibodies but not by anti-hMYH peptide antibodies. Together with the previously described mitochondrial MutT homolog (MTH1) and 8-oxoG glycosylase (OGG1, a functional MutM homolog), mtMYH can protect mitochondrial DNA from the mutagenic effects of 8-oxoG.

Animals↗

Control of response selection by reinforcer value requires interaction of amygdala and orbital prefrontal cortex.

Goal-directed actions are guided by expected outcomes of those actions. Humans with bilateral damage to ventromedial prefrontal cortex, or the amygdala, are deficient in their ability to use information about positive and negative outcomes to guide their choice behavior. Similarly, rats and monkeys with orbital prefrontal or amygdala damage have been found to be impaired in their responses to changing values of outcomes. In the present study, we tested whether direct, functional interaction between the amygdala and the orbital prefrontal cortex is necessary for guiding behavior based on expected outcomes. Unlike control monkeys, rhesus monkeys with surgical disconnection of these two structures, achieved by crossed unilateral lesions of the amygdala in one hemisphere and orbital prefrontal cortex in the other, combined with forebrain commissurotomy, were unable to adjust their choice behavior after a change in the outcome (here, a reduction in the value of a particular reinforcer). The lesions did not affect motivation to work for a food reinforcer, or food preferences, per se. Hence, the amygdala and orbital prefrontal cortex act as part of an integrated neural system guiding decision-making and adaptive response selection.

Accommodation, Ocular↗

The distribution of micro-organic contaminants in river bed-sediment cores.

There is little information available on the distributions of micro-organic contaminants in river bed-sediments below a depth of 5 cm. The aim of this study is to determine the concentrations and distributions of contaminants in river bed-sediments up to 1 m depth and to make an assessment of the results. The approach taken was to collect five cores from each of two lowland rivers in southern England, the first a rural river and the second a dominantly urban catchment. The cores were analysed for micro-organic compounds and sediment/sediment porewater characteristics. Compounds detected were polyaromatic hydrocarbons (naphthalene, fluoranthene and pyrene), pesticides (carbaryl, linuron, fenpropimorph, the synthetic pyrethroids, and prometryn), and non-ionic surfactant residue (nonylphenol). A particularly important finding was that some micro-organic contaminants penetrated to depths of 1 m, and in one of the rivers they were detected in undisturbed Eocene substrata. The more hydrophobic contaminants showed a clear depth distribution with higher concentrations towards the top of the cores. The less hydrophobic contaminants demonstrated no systematic trend suggesting they had become soluble in porewaters and subsequently travelled within the cores. Partition between the porewater and sediment appeared to be controlling the distribution of the compounds with depth.

England↗

Preliminary evidence for the existence of specific functional assemblies between enzymes of the beta-oxidation pathway and the respiratory chain.

The electron-transferring flavoprotein (ETF) has been detected in two large soluble-protein complexes partially purified from sonicated porcine liver mitochondria. Size-exclusion chromatography and sucrose-density ultracentrifugation suggested molecular masses in the region of 390 to 420 kDa for the two complexes. Activities of medium-chain acyl-CoA dehydrogenase, sarcosine dehydrogenase and ETF:ubiquinone oxidoreductase were also detected. No evidence of oxidative-phosphorylation properties was obtained. Treatment with antimycin A inhibited the activity of both complexes. Pyridine haemochromogens, prepared from the partially purified species, show the presence of cytochrome proteins. The possible composition of these complexes and their relationship to the electron transport chain are discussed.

Acyl-CoA Dehydrogenase↗

Mediodorsal thalamic function in scene memory in rhesus monkeys.

Three monkeys were trained preoperatively in a scene memory task which is analogous, in some ways, to human episodic memory. The same animals were also trained in object-reward association memory. Following bilateral ablations of almost the entire magnocellular division of the mediodorsal thalamic nucleus, the animals were impaired both in scene memory and in object-reward association memory. These results, combined with recent results in object recognition memory from monkeys with mediodorsal thalamic lesions, show that the impairment produced by this lesion is more general, affecting a broader range of memory tasks, than the impairment which is produced in monkeys by lesions restricted to the hippocampus-fornix-mamillary system. It is also more severe than the effect of lesions limited to the medial part of the magnocellular division of the mediodorsal thalamic nucleus. These findings extend the evidence that the magnocellular division of the mediodorsal thalamic nucleus has an important and general role in memory, and they are consistent with the proposal that lesions of the magnocellular division of that nucleus have their effect by disrupting the function of prefrontal cortex.

Animals↗

Fludarabine induced intestinal pseudo-obstruction: case report and literature review.

Intestinal pseudo-obstruction is a recognized but rare complication of chemotherapy. Vinca alkaloids and cytarabine have been reported to be associated with intestinal pseudo-obstruction. We report a case of fludarabine induced severe intestinal pseudo-obstruction in a 66-year-old man suffering from non-Hodgkin's lymphoma, and describe our successful management of this with a combination of parasympathomimetic and mechanical decompression, after failure of conservative management.

Aged↗

Effect of short-term feed restriction and calorie source on hormonal and metabolic responses in geldings receiving a small meal.

The metabolic effects of short-term feed restriction and dietary calorie source were studied in horses receiving high-roughage or high-concentrate diets. Four Thoroughbred geldings were assigned to four treatment groups in a 4 x 4 Latin square experiment. The four treatments were 1) a nutritionally adequate high-roughage ration (70% roughage, 30% concentrate; AHR), 2) a nutritionally adequate high-concentrate ration (40% roughage, 60% concentrate; AHC), 3) 70% of the intake of the AHR diet (RHR), and 4) 70% of the intake of the AHC diet (RHC). Diets AHR and AHC were designed to meet the caloric need of horses undergoing moderately intense work. Blood samples were taken on the first 7 d of each period for analysis of serum T4 and T3 concentrations. On d 9 of each feeding period, each horse was fed 1.0 kg of oats as the morning meal. Jugular blood was sampled before and immediately after, as well as at 30 min after, completion of the meal and subsequently every hour for 7 h. Daily serum T4 and T3 concentrations were not affected by day, feeding level, or diet composition. Meal feeding produced an increase (P < 0.01) in T4 and T3 concentrations when horses were adapted to the AHR and AHC diets but not the RHR or RHC diets. Thyroxine concentrations were lowest (P < 0.05) when horses were adapted to the AHC diet. Glucose (P < 0.05), insulin (P < 0.01), and NEFA (P < 0.01) concentrations were higher in response to the meal when horses received RHR than for the other diets. These results indicate that nutrient restriction alters responses to meal feeding in horses and that this response may also be affected by the dietary roughage:concentrate ratio.

Animal Feed↗

CNS involvement of virus-associated hemophagocytic syndrome: MR imaging appearance.

The MR imaging appearance of a case of virus-associated hemophagocytic syndrome complicated by diffuse CNS infiltration is presented. Virus-associated hemophagocytic syndrome is a rare condition, precipitated by viral infection and characterized by proliferation of benign histiocytes with phagocytosis. In severe cases, the CNS may be involved.

Adult↗

Mycobacterium avium interaction with macrophages and intestinal epithelial cells.

Mycobacterium avium is an environmental microorganism that is adapted to live both in the environment (mainly in water and soil) and in bird, fish and mammal hosts. In humans, M. avium infection is seen in patients with some sort of immunosuppression, such as patients with chronic lung disease, and Acquired Immunodeficiency Syndrome. More recently, other populations were shown to be at risk to develop M. avium disease. For the majority of time, humans acquire M. avium through the intestinal tract where the bacterium comes in contact with and translocates the intestinal mucosa. M. avium possesses a unique manner to interact with the intestinal mucosa, and, following invasion, can enter and survive within macrophages and monocytes. Although in vitro entry seems to be dependent on binding to the complement receptor, this finding has not been observed in vivo where the bacterium appears to enter macrophages by alternative mechanisms. The bacterium appears to trigger little inflammatory response, and is able to adapt itself to different environments in the host.

Bacterial Translocation↗

Apoptosis of Mycobacterium avium-infected macrophages is mediated by both tumour necrosis factor (TNF) and Fas, and involves the activation of caspases.

Mycobacterium avium causes disseminated infection in AIDS patients and several forms of infection in immunocompetent hosts. Recent studies have shown that M. avium infection of macrophages in vitro leads to apoptosis of significant numbers of infected cells. Several strains of M. avium used to infect human macrophages for 5 days (multiplicity of infection of 10) triggered 28-46% higher levels of apoptosis than observed with uninfected macrophages at the same time points. Mycobacterium avium strains unable to replicate intracellularly (rep-) resulted in a 15% rate of apoptosis, while M. smegmatis-infected monolayers showed the same percentage of apoptotic cells as the uninfected macrophage control. The presence of anti-TNF-alpha antibody reduced apoptosis to 17% and the presence of anti-Fas antibody reduced apoptosis to 10%. When both antibodies were used together, the apoptosis level was 5% above the control. Treatment with TGF-beta also reduced the number of apoptotic cells in infected monolayers. If intracellular growth was inhibited, apoptosis of macrophages decreased significantly. It was also shown that apoptosis was associated with IL-1 beta-converting enzyme (ICE) activation and was significantly reduced by a caspase inhibitor. Gaining understanding of the mechanisms of M. avium-associated apoptosis of macrophages will provide important insight into M. avium pathogenesis.

Apoptosis↗

Left ventricular remodelling in post-myocardial infarction patients with left ventricular ejection fraction 40-50% vs 25-39%. Influence of nisoldipine treatment? An echocardiographic substudy from the DEFIANT II study.

OBJECTIVE: Left ventricular (LV) remodelling following acute myocardial infarction has generally been studied in patients with LV ejection fraction (EF) < 40%, and it has been shown that this process can be attenuated by ACE inhibitors. Little is known regarding LV remodelling in patients with LVEF > or = 40% or the effects of treatment in this patient cohort. The DEFIANT II study (Doppler Flow and Echocardiography in Functional cardiac insufficiency) included 542 post-infarction patients with LVEF 25-50% without overt heart failure within 13 days following acute myocardial infarction (AMI). They were then randomized to nisoldipine coat-core (CC) or placebo and followed up for 6 months. DESIGN: Two-dimensional echoes were obtained after 8 (5-13) days and 6 months following AMI. SETTING: LV end diastolic (ED) and end systolic (ES) volumes (V) were calculated in 503 patients with technically satisfactory paired echoes using the biplabe method of discs in a core laboratory. SUBJECTS: Group A. 217 patients with baseline EF 40-50%, of whom 112 were randomized to nisoldipine and 104 to placebo (one patient was taken off study medication). Group B. 286 patients with EF 25-39%, of whom 145 were randomized to nisoldipine and 141 to placebo. RESULTS: LVEDV was 175 (+/-45) ml in Group A vs 203 (+/-49) ml in Group B (p = 0.001) at baseline and 184 (+/-48) ml vs 213 (+/-56) ml (p = 0.001), respectively, at 6 months. LVESV at baseline was 97 (+/-42) ml in Group A vs 133 (+/-37) ml in Group B (p = 0.001), and 106 (+/-34) ml vs 134 (+/-45) ml (p = 0.001) at 6 months, respectively. The increase of LVESV was 9 (+/-29) ml in Group A vs 2 (+/-35) ml in Group B (p = 0.007). LVEF decreased by 2 (+/-6)% in Group A vs an increase of 3 (+/-6)% in Group B (p = 0.001). Treatment with nisoldipine had no influence on LV volumes in either of the two groups or in the total study group. CONCLUSION: LV dilatation 6 months following AMI in patients with EF 40-50% was similar in end diastole, but more pronounced in end systole vs patients with EF 25-39%. LV remodelling did not change significantly after nisoldipine treatment.

Adult↗