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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 253 records · Page 14Linked to original sources

Effect of intracoronary saline infusion on dissection during excimer laser coronary angioplasty: a randomized trial. The Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Investigators.

OBJECTIVES: We sought to evaluate whether intracoronary saline infusion during excimer laser coronary angioplasty decreases the incidence of significant laser-induced coronary artery dissections. BACKGROUND: Despite procedural success rates > 90%, coronary artery dissections occur in 17% to 27% of excimer laser coronary angioplasty procedures. Excimer laser irradiation of blood results in vapor bubble formation and acoustomechanical trauma to the vessel wall. Saline infusion into a coronary artery may minimize blood irradiation and consequent arterial wall damage. METHODS: In this prospective, randomized, controlled study, consecutive patients undergoing excimer laser coronary angioplasty were randomly assigned to conventional laser irradiation in a blood medium or to laser irradiation with blood displacement by intracoronary saline infusion. In the patients randomized to intracoronary saline infusion, prewarmed normal saline was injected through the coronary artery guide catheter at a rate of 1 to 2 ml/s using a power injector. The incidence and severity of dissection after excimer laser ablation were evaluated in a core laboratory by angiographers with no knowledge of treatment assignment. The severity of coronary artery dissection was rated on an ordinal scale of 1 to 5. Dissections of grade 2 or higher were considered significant. RESULTS: The mean (+/- SE) dissection grade after laser angioplasty in patients treated with intracoronary saline infusion was 0.43 +/- 0.13 compared with 0.91 +/- 0.26 in patients undergoing laser angioplasty in a blood medium. The incidence of significant dissection was 7% in saline-treated patients compared with 24% in conventionally treated patients (p < 0.05). No significant complications were associated with saline infusion. CONCLUSIONS: Intracoronary saline infusion should be incorporated into all excimer laser coronary angioplasty procedures.

Aged↗

Microsomal triglyceride transfer protein activity remains unchanged in rat livers under conditions of altered very-low-density lipoprotein secretion.

Microsomal triglyceride transfer protein (MTP) is a heterodimeric protein consisting of a unique 97 kDa subunit and protein disulphide isomerase, that mediates the transfer of lipid between membranes and nascent lipoproteins. Mutations in the gene encoding the 97 kDa subunit of the protein cause the rare autosomal recessive disorder abetalipoproteinaemia. Recent findings in cultured cells indicate that the 5' promoter region contains an insulin-responsive element, suggesting that the gene is responsive to insulin regulation. In this study we examined two cases where very-low-density lipoprotein (VLDL) secretion is markedly reduced: the streptozotocin-diabetic rat and 10-day-old suckling rats. In both cases MTP activity was unaltered compared with that in control animals. Equal levels of MTP were also apparent in the livers of all groups of animals, as measured by immunoblotting with an anti-MTP antiserum. These findings indicate that factors other than MTP activity are responsible for the reduction in hepatic VLDL triglyceride secretion observed in the suckling and diabetic animals.

Animals↗

Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.

The site-specific C to U editing of apolipoprotein B100 (apoB100) mRNA requires a 27 kDa protein (p27) with homology to cytidine deaminase. Here, we show that p27 is a zinc-containing deaminase, which operates catalytically like the E. coli enzyme that acts on monomeric substrate. In contrast with the bacterial enzyme that does not bind RNA, p27 interacts with its polymeric apoB mRNA substrate at AU sequences adjacent to the editing site. This interaction is necessary for editing. RNA binding is mediated through amino acid residues involved in zinc coordination, in proton shuttling, and in forming the alpha beta alpha structure that encompasses the active site. However, certain mutations that inactivate the enzyme do not affect RNA binding. Thus, RNA binding does not require a catalytically active site. The acquisition of polymeric substrate binding provides a route for the evolution of this editing enzyme from one that acts on monomeric substrates.

APOBEC-1 Deaminase↗

Studies on the translocation of the amino terminus of apolipoprotein B into the endoplasmic reticulum.

Apolipoprotein (apo) B is either co-translationally assembled into lipoproteins, or becomes associated with the membrane of the endoplasmic reticulum (ER) and is subsequently degraded. It has been proposed that apoB undergoes a novel process of translocation which generates cytoplasmically exposed apoB in the ER of hepatic and non-hepatic cells. Transmembrane forms of apoB can also be generated by in vitro translation (Chuck, S. L., and Lingappa, V. R. (1992) Cell 68, 9-21), which might explain the origin of untranslocated apoB in vivo. Here we have investigated a protocol which generates transmembrane forms of apoB during in vitro translation of truncated RNA transcripts. We observe that apoB can become transmembrane at sites of ribosome pausing and be held in this configuration by persistence of tRNA on the peptide chains. Ribosome pausing also occurs at these same sites in the absence of acceptor microsomes. Transmembrane topology can be generated at sites of ribosome pausing in a cytosolic protein, sea urchin cyclin when fused to a signal sequence. Mapping of the ribosome pause sites in apoB and in cyclin revealed no amino acid sequence homology. Chimeric constructs with engineered downstream glycosylation sites showed no evidence that ribosome pause sequences affect translocation of transcripts with termination codons. Transmembrane forms of apoB and cyclin were not generated during translocation into the ER in transfected COS cells.

Amino Acid Sequence↗

The relationship between premorbid neuroticism, cognitive dysfunction and persistence of depression: a 1-year follow-up.

In a previous report of patients with unipolar major depressive disorder, we found that deficits in autobiographical memory predicted depression levels over a 7-month interval. This follow-up examined predictors of recovery as defined by a period of 8 weeks with no or minimal symptoms of depression and examined the extra predictor variable, neuroticism. In a sample of 21 patients, episode duration was significantly correlated with high levels of premorbid neuroticism, dysfunctional attitudes and overgeneral autobiographical memories produced in response to emotionally negative cue words. When severity of depression was partialled out, high N score was significantly but independently correlated with each of these cognitive variables. The implication of these attitudinal and information processing biases were explored.

Adult↗

The AMP-activated protein kinase gene is highly expressed in rat skeletal muscle. Alternative splicing and tissue distribution of the mRNA.

The AMP-activated protein kinase (AMPK) phosphorylates, and thereby inactivates, a number of enzymes involved in the regulation of lipid metabolism. We have studied the expression of the AMPK gene in a variety of rat tissues. The gene is transcribed into a message of approximately 9.5 kb as detected by Northern blotting. Highest expression of the AMPK message was found in skeletal muscle, which contained 20 amol/micrograms total RNA as determined by competitive reverse-transcription/polymerase chain reaction (RT-PCR). In liver, kidney, brain, mammary glands, heart and lung, AMPK mRNA levels ranged over 1-4 amol/micrograms total RNA. Adipose tissue contained less than 1 amol/microgram total RNA. A second AMPK mRNA form was detected by RT-PCR that was 142 bases shorter than the functional transcript. This transcript was apparently generated by alternative splicing of a single exon within the 5'-coding region. The shorter of the two messages, which is not translated into AMPK protein, contributed between 35-60% of AMPK mRNA in most tissues, but only 15-20% in skeletal muscle and heart. As a result, functional AMPK mRNA was sevenfold higher in skeletal muscle than in liver, although AMPK activity was much lower. By Western blotting, relatively large amounts of AMPK protein were detected in skeletal muscle compared to liver. AMPK isolated from skeletal muscle was not activated by treatment with AMPK kinase under conditions where liver AMPK was fully activated. A single 63-kDa polypeptide was immunoprecipitated from rat skeletal muscle using anti-peptide IgG against AMPK. In contrast, two additional polypeptides with apparent molecular masses of 38 kDa and 36 kDa co-precipitated with the 63-kDa AMPK protein from rat liver. These results indicate that the muscle enzyme has a different subunit organization compared to the liver enzyme, which may account for its low catalytic activity. Together, our results indicate a physiological role for AMPK in muscle, in addition to its previously described role in lipid metabolism.

AMP-Activated Protein Kinases↗

Detection of low-grade mosaicism in fetal cells isolated from maternal blood.

Recovering and analysing fetal erythrocytes from maternal blood is being pursued for non-invasive prenatal genetic diagnosis. We report the observation of 46,XY/47,XXY mosaicism in fetal cells from a woman whose first-trimester chorionic villus sampling (CVS) initially showed only 46,XY. Only after exhaustive (500 cells) analysis were four XXY cells found in cultured villi.

Adult↗

Rate of oxygen consumption by parotid atrophic acinar cells from rats fed liquid diet.

Adult male rats were maintained on a nutritionally adequate liquid-diet or laboratory chow and water (control), for 9 days. They were then killed and the parotid glands removed. Enzymatically dispersed acinar-cell preparations were used to study rates of oxygen consumption (QO2) using a Clark oxygen electrode. For both CON and LD cell preparations the basal QO2 was 0.132 (+/- 0.03-0.05) nmol O2 per microgram DNA per min and in each case this was increased approx. 2.4-fold under stimulation by carbachol (10 microM) and approx. 3.1-fold by adrenaline (10 microM). Isoprenaline (10 microM) elicited no significant increase in QO2. Addition of ouabain (2.5 mM) or removal of Ca2+ from the extracellular medium prevented the action of carbachol to increase QO2 over a sustained period. There were no significant differences in the basal, agonist-stimulated, or ouabain-sensitive QO2 by dispersed acinar cells from liquid-diet rats compared to control. The results are consistent with the notion that liquid diet-induced atrophy represents a physiological adaptation rather than a pathological change. Nevertheless, they also indicate that in the acinar cells from liquid-diet rats the Na+/K+ ATPase is required to operate at normal levels of energy consumption despite the reduced acinar-cell volume and consequently lower levels of agonist-elicited transepithelial ion movements known to occur in these cells.

Animal Feed↗

A 31p-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs.

To evaluate the effect of hypothermic circulatory arrest on brain metabolism, we used 31P-magnetic resonance spectroscopy to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion. Twenty-eight pigs were divided into five groups. Anesthesia (n = 5) and hypothermic cardiopulmonary bypass groups (n = 5) served as controls. In the circulatory arrest (n = 6), antegrade perfusion (n = 6), and retrograde (n = 6) brain perfusion groups, the bypass flow rate was 60 to 100 ml.kg-1.min-1. In the antegrade group, the brain was perfused via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C. The intracellular pH was 7.1 +/- 0.1 and 7.3 +/- 0.1 in the anesthesia and hypothermic cardiopulmonary bypass groups, respectively. In the circulatory arrest group, the intracellular pH decreased to 6.2 +/- 0.1 and did not recover to its initial value (7.0 +/- 0.1) during reperfusion (p < 0.05 compared with the value obtained from the control groups at the corresponding time). Inorganic phosphate did not return to its initial level during reperfusion. In three animals in this group, levels of high-energy phosphates, adenosine triphosphate and phosphocreatine, recovered partially but did not reach the levels observed before arrest. In the group receiving antegrade perfusion, cerebral metabolites and intracellular pH were unchanged throughout the protocol. During circulatory arrest in the retrograde perfusion group the intracellular pH decreased to 6.4 +/- 0.1 and recovered fully during reperfusion (7.1 +/- 0.1). High-energy phosphates also returned to their initial levels during reperfusion. These studies show that deep hypothermic circulatory arrest with antegrade brain perfusion provides the best brain protection of the options investigated.

Adenosine Triphosphate↗

Correlation of histopathologic findings with clinical and radiologic assessments of cervical lymph-node metastases in oral cancer.

The accuracy of preoperative diagnosis of cervical lymph-node metastasis in oral cancer was assessed by comparing the histopathologic findings in 136 sides of neck dissection with physical examination under anaesthesia (EUA) and computerized tomography (CT) assessments of the metastatic status. The overall accuracy of EUA and CT assessments was 72% and 73%, respectively, and a combination of both methods resulted in sensitivity and specificity rates of 55% and 78%, respectively. Twenty-three of the 51 histologically positive necks had been assessed as negative on both EUA and CT. Six of these contained only micro-metastases, and in another 10, the largest positive node was 1.5 cm or less. Extracapsular spread of metastatic carcinoma was found in 12 of the 23 EUA and CT false-negative dissections. Most of the 21 histologically positive necks which had been correctly assessed as positive on both EUA and CT contained enlarged metastatic nodes, fused nodal masses, extensive extracapsular spread, or more than one of these features. Three of the 85 histologically negative necks had been assessed as positive on both EUA and CT; eight had been positive on EUA alone, and another eight on CT alone. Reactive nodal hyperplasia or sialadenitis was seen in most false-positive dissections. We conclude that the accuracy of preoperative diagnosis of metastasis by routine methods remains poor, and that EUA and CT are reliable only in patients with bulky metastatic deposits.

Adolescent↗

Desmoplastic trichoepithelioma of the upper lip. A case report with histochemical features and observations on its histogenesis.

A case of desmoplastic trichoepithelioma of the upper lip investigated by histochemistry and immunocytochemistry is presented. There was histologic suggestion of cytoplasmic vacuolation that does not appear to have been previously described. Histochemical examination indicated the presence of glycogen within tumor cells and a reparative-type stroma. Immunocytochemical examination revealed variable reactivity for high molecular weight cytokeratin and colonization by Langerhans' cells. The observations suggest a follicular and sudoriferous differentiation for desmoplastic trichoepithelioma and hence an origin from a pluripotential adnexal keratinocyte.

Female↗

Psychotherapy for bipolar disorder.

BACKGROUND: Psychosocial factors may contribute 25-30% to the outcome variance in bipolar disorders. Sufferers have identified benefits from psychotherapy, but biological models and treatments dominate the research agenda. The author reviews research on psychosocial issues and interventions in this disorder. METHOD: Research on adjustment to the disorder, interpersonal stressors and obstacles to treatment compliance were located by computerised searches and the author's knowledge of the literature. All published outcome studies of psychosocial interventions in bipolar disorder are reviewed. RESULTS: There is an inadequate database on psychosocial factors associated with onset and maintenance of bipolar disorder. While the outcome studies available are methodologically inadequate, the accumulated evidence suggests that psychosocial interventions may have significant benefits for bipolar sufferers and their families. CONCLUSIONS: Given the significant associated morbidity and mortality, there is a clear need for more systematic clinical management that addresses psychosocial as well as biological aspects of bipolar disorder. The author identifies appropriate research strategies to improve knowledge of effective psychosocial interventions.

Adaptation, Psychological↗

Operational aspects of Quality-of-Life Assessment. Choosing the right instrument.

In assessing quality of life, the most important goal is to develop a strategy that produces useable and useful information for decision making. Assessment design is complex, and whether an assessment is developed from scratch, or 1 or more portions of existing instruments are adapted, the focus must be on the quality of the theoretical and operational elements of the particular line of inquiry and its environment. The necessary and most often discussed focus on the theoretical dimensions of validity, reliability and responsiveness is not sufficient to insure that the data are of the requisite high quality. There is also a need, almost universally given little attention in the literature, to look at operational aspects, such as design, format, flow, appearance, and response-stimulus, of each assessment instrument. Searching for guidance in the quality-of-life (QOL) literature remains a challenge even with computers, modems, keywords, static guidebooks and bibliographic systems. The On-Line Guide to Quality-of-Life Assessments (OLGA) is presented as a personal computer-based system that is updated 3 times a year to provide QOL researchers and assessment developers with 2 databases: assessments providing full descriptions and contact information; and references providing fully keyed citations to the assessment use literature. These databases are made more useful by decision-logical programs that identify relevant assessments and supporting research literature. OLGA can thus save time and other resources by helping investigators concentrate on the most relevant elements of the existing literature. This focus will assist them in avoiding the problems of ending up with the right answers to the wrong questions.

Health Status↗