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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 343 records · Page 19Linked to original sources

Apolipoprotein B mRNA editing: a new tier for the control of gene expression.

Two forms of apolipoprotein (apo) B are found in mammals. The shorter form is translated from an edited mRNA in which a specific cytidine base is deaminated to a uridine, creating a new stop codon. Apo B mRNA editing is mediated by a site-specific cytidine deaminase that recognizes a downstream target sequence in the RNA. The enzyme has no energy or cofactor requirements and no RNA component, and thus bears no obvious relationship to RNA processing events such as splicing or polyadenylation. While apo B mRNA editing activity may have arrived late in evolution to target dietary lipid to the liver in mammals, the discovery of the editing activity in tissues and cells that do not express apo B suggests a more widespread role in the generation of RNA and protein diversity.

Animals↗

Suprarenal Greenfield filter placement to prevent pulmonary embolus in patients with vena caval tumor thrombi.

The presence of tumor thrombus secondary to inferior vena caval extension from renal carcinoma carries the threat of pulmonary tumor embolus. In theory, safe prophylaxis could be accomplished by placement of a Greenfield filter in the suprarenal vena cava, which has been accomplished without complication. We treated 6 patients with renal call carcinoma and extensive tumor thrombus of the vena cava with suprarenal filter placement as an adjunct to thrombectomy and nephrectomy. Clinically all 6 patients have done well. However, the over-all rate of vena caval thrombosis or occlusion associated with infrarenal filter placement is 3 to 5%. To investigate the potential risk to renal function if a vena caval occlusion occurred above a solitary kidney shortly after unilateral nephrectomy, we performed suprarenal inferior vena caval ligations after unilateral nephrectomy in 10 dogs. A total of 6 dogs suffered persistent loss of renal function and 3 of these 6 died of uremia. Of 4 dogs who underwent suprarenal inferior vena caval ligation only 1 (25%) had persistent compromise of renal function. A total of 2 dogs underwent unilateral nephrectomy only without compromise of normal renal function. We conclude that the risk of total vena caval occlusion after suprarenal Greenfield filter placement is small. However, should it occur in the setting of recent nephrectomy there is potential for significant renal morbidity. In selected patients this risk may be offset by the potential benefits that the filter offers in terms of protection against tumor and/or bland pulmonary embolus. Further clinical experience will be needed to strengthen and clarify the indications and benefits of preoperative or intraoperative filter placement as reported.

Adult↗

Multiple authorship in two English-language journals in radiation oncology.

Multiple authorship is the listing of more than one person as author of an article in the scholarly literature. Editors, researchers, and others in science publishing have raised concerns about the increasing number of authors being listed per article, the practice of "honorary authorship" (listing as an author someone who made little or no contribution to the work being reported), and the danger of the dilution of responsibility when many authors are involved. The authors studied multiauthorship in the two most popular English-language journals on radiation oncology, examining 1,908 papers and letters published in the International Journal of Radiation Oncology, Biology, and Physics (IJROBP) and Radiotherapy and Oncology (RO) from 1983 through 1987. There was no increase in the number of authors per article during this period, when the median number for IJROBP was four and that for RO was three. The number of authors varied by type of article, by country (France had the largest median number, six for IJROBP and five for RO), and by the authors' institution. The first author's gender was unrelated to the number of subsequent authors for an article. The proportion of men first authors varied widely between countries and institutions. Possible explanations for these variations include the multidisciplinary nature and complexity of some forms of research, institutional policies concerning the use of authorship as a commodity of exchange, and social-cultural factors.

Authorship↗

Primary Care Health Information System: a hybrid electronic-paper medical record system.

In summary, PCHIS is a hybrid electronic-paper medical record system that is clinically useful to health care providers. The paper chart still contains the bulk of information but the key facts about any given patient (diagnoses, surgeries, medications, allergies) and about the process of care (frequency of visits, referral patterns, test ordering, etc.) are readily available in electronic form. These key data are easily coded, are quickly and simultaneously accessible in multiple locations, serve as an excellent chart substitute whenever the paper chart is unavailable, and can be retrieved for in-depth analysis at any time, whether for clinical, administrative, research, or quality assurance purposes. The process of care can be studied and, to some extent, can also be modified by the system, as demonstrated by the physician response to the reminder system within PCHIS. The medical record chart summary, mandated by Joint Commission for ambulatory patient charts, is easily provided in hard copy as well as electronically. Whereas physician compliance in providing data to the system was initially sporadic, physician support has increased tremendously as the system has become more clinically useful to them. It is a system that exists and functions well within a patchwork of multiple different medical information systems. It is a system with sufficient intrinsic flexibility that it can and will continue to evolve in response to the needs of physicians and administrators.

Academic Medical Centers↗

Characterization of cultured human nesidioblasts and their associated macromolecules: cross-reactivity with a cloned rat pancreatic beta-cell line.

Near-total pancreatectomy in a neonate presenting with persistent hypoglycemia offered an unusual opportunity to grow preparations enriched in beta-cells. Morphology, chromosomal analysis, and immunohistochemistry were used to characterize a subculture (Nesi B) that remained stable through passage 11. Insulin secretion of Nesi B was constitutive at 38-74 nU/microliters of medium/24 h, increasing modestly in the presence of isobutylmethylxanthine, an inhibitor of cyclic AMP phosphodiesterase. Endocrine cells, exclusive of those in islet regions, were widely distributed throughout the original tissue section, and immunostaining of the Nesi B subculture demonstrated well-differentiated heavily granulated insulin-positive cells, each with a normal modal number of chromosomes (46). Nesi B cell-associated macromolecules were isolated in 3 x 10(-3) ethylenedinitrilotetraacetate/phosphate-buffered saline and were found to be reactive with a heterologous immune serum elicited to a cloned rat pancreatic beta-cell line (RIN-5F). Western (immuno) blotting showed this immunoreactivity to reside primarily in a 95-kDa fraction of Nesi B-derived components. These results indicate that human nesidioblasts can be cultured for a sufficient number of passages to allow isolation and immunochemical characterization of pancreatic beta-cell macromolecules shared between rat and human and that may serve as organ-specific antigens for inflammatory disorders of the pancreas.

Animals↗

Audiological evaluation of very low birthweight infants.

A population of consecutively surviving very low birthweight (VLBW) infants comprising 41 infants (24 female) birthweight less than 1000 g and 108 infants (63 female) birthweight 1000-1500 g received detailed audiological evaluation. The audiological test battery comprised auditory brainstem evoked response (ABR) prior to hospital discharge, behavioural audiometry and tympanometry at 8-12 months and monitoring as necessary. The ABR results were interpreted with reference to a normative group of 36 full-term infants (birthweight 2.4-4.5 kg). Of the 142 VLBW infants completing audiological evaluation, one (0.7%) had evidence of moderate-severe high frequency sensorineural hearing loss, 83 (58.5%) evidence of conductive dysfunction (18 severe, 42 moderate and 23 mild) and only 58 (40.8%) normal hearing. The 19 infants with severe auditory impairment were more likely to have suffered moderate-severe apnoea, greater than or equal to two courses of mechanical ventilation, prolonged oxygen therapy and recurrent upper respiratory tract infections in the first year of life than infants without severe impairment (P less than 0.05). Because of the incidence of conductive pathology, difficulties occurred when attempting to compare ABR status at 36-42 weeks postmenstrual age with peripheral hearing status at 8-12 months as assessed by visual reinforcement orientation audiometry (VROA) and impedance audiometry. The most useful ABR test parameters as screening measures of peripheral auditory status were Wave I-III-V morphology, wave V threshold levels and wave V absolute latency values when used in combination as a test battery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Impedance Tests↗

Detection of fetal DNA in trans-cervical swabs from first trimester pregnancies by gene amplification: a new route to prenatal diagnosis?

OBJECTIVE: To determine whether fetal sex can be predicted from fetal DNA retrieved transcervically from the lower part of the uterine cavity in the first trimester of pregnancy. DESIGN: Prospective observational study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 33 women undergoing legal termination of pregnancy at 9 to 13 weeks gestational age. INTERVENTIONS: Before termination of pregnancy samples for DNA analysis were obtained with cotton wool swabs from the vagina, cervix and transcervically in 26 women. In the other seven women samples were obtained using a transcervical cell retrieval (TraCeR) procedure involving flushing the lower uterine cavity with 5 ml saline. MAIN OUTCOME MEASURES: Detection of Y-chromosome specific DNA sequences by the polymerase chain reaction (PCR) in cotton wool swabs taken from the lower uterus in the first trimester of pregnancy to predict fetal sex in comparison with standard cytogenetic analysis. Histological and immunohistochemical analysis of samples obtained by flushing of the lower uterine cavity (TraCeR) to confirm the presence of trophoblast. RESULTS: Fetal sex was predicted accurately in 25 of the 26 pregnancies investigated. Immunohistochemical analysis identified syncytial trophoblast fragments in all seven pregnancies investigated by TraCeR. CONCLUSION: Trophoblast may be retrieved from the lower uterus in the first trimester by swabs or TraCeR. When purification of these syncytial fragments can be achieved using immuno-magnetic technology, this test will enable prenatal diagnosis of single gene defects in the fetus by the polymerase chain reaction.

Cervix Uteri↗

Coronary occlusive disease and late graft failure after cardiac transplantation.

OBJECTIVE: Coronary occlusive disease is the main cause of late mortality after cardiac transplantation. It has both similarities and differences compared with conventional atherosclerotic coronary disease. The pathophysiology of late graft failure from coronary occlusive disease is unclear at present. We reviewed the experience of this disorder in our cardiac transplant programme. DESIGN: A retrospective analysis of angiographic and pathological data. SETTING: A regional cardiothoracic centre and transplant unit. PATIENTS: Of a population of 383 orthotopic cardiac transplant recipients operated upon between January 1979 and June 1990, 447 coronary angiograms were available for review in 193 patients. Thirteen of a possible 18 results of post mortem examinations from patients dying from coronary occlusive disease were available. MAIN OUTCOME MEASURE: Coronary occlusive disease was defined as any evidence of disease on coronary angiography. Post mortem examinations were performed with standard techniques. RESULTS: The angiographic prevalence of coronary occlusive disease was 3% (1/32 patients) and 40% (19/47 patients) at one and five years respectively. Twenty six grafts failed due to coronary occlusive disease compared with 132 graft failures from all causes during this period. Acute thrombosis was present in a large vessel in seven of 13 fatal cases undergoing necropsy (54%). Noticeable large vessel involvement with disease in smaller distal vessels was present in four patients (31%). The remaining two patients (15%) had small vessel disease alone. Twelve of the 13 patients had significant cardiomegaly (cardiac weight > or = 400 g) with a mean weight of 510 (range 370-740) g. CONCLUSION: Coronary occlusive disease is the main late complication after cardiac transplantation. A combination of coronary thrombosis, ischaemia from stenoses of large and small coronary vessels, and cardiomegaly contribute to the graft failure of these patients.

Adolescent↗

Renin and angiotensinogen expression during the evolution of diabetes.

The expression of renin and angiotensinogen genes and their proteins were studied during the progression of diabetes using adult BioBreeding spontaneously diabetic rats at 1 day and 2-12 months of diabetes. The number of renin-stained cells per juxtaglomerular apparatus was determined by immunocytochemistry. Initially, at 2 months of diabetes the number of renin-stained cells per juxtaglomerular apparatus increased significantly (p less than 0.0001, 2 months versus resistant groups) and was followed by a decrease in the number and intensity of renin-stained cells after 12 months of diabetes (p = 0.007, 2 months versus 12 months). A significant negative correlation was observed between the number of renin-containing cells and the duration of diabetes (r = 0.99, p = 0.014). Immunoreactive angiotensinogen was restricted to the proximal tubule and appeared increased after 4 and 8 months of diabetes as compared with the 2- and 12-month diabetic groups. Renin messenger RNA (mRNA) levels increased with the onset of diabetes and decreased markedly during chronic diabetes. At 1 day of diabetes, renin mRNA levels were 700% higher than at 12 months of diabetes. Angiotensinogen mRNA levels were unchanged. We conclude that diabetes results in an initial increase in renin gene expression, and as the duration of diabetes lengthens, there is a progressive decrease in renin gene expression and in the number of cells containing renin. These findings suggest that as the duration of diabetes and the age of the animal lengthens, there is a decrease in the number of cells expressing the renin gene.

Angiotensinogen↗

Can we predict the persistence of depression?

Fifty-five patients with primary major depression were followed up prospectively from time of onset of the index illness episode until recovery. The course of depression in hospital-treated patients was protracted, with a median length of episode of one year. Two factors significantly predicted persistence of symptoms: interval between onset and receipt of treatment, and premorbid neuroticism, which accounted for 55% of the variance in length of episode.

Adult↗

Experience with the Astra dental implant system.

The Astra Dental Implant System appears to be a relatively successful and economical method of osseointegration. This article lists its clinical components, explains how the system is fitted and discusses the preliminary results.

Aged↗

Temporal lectin histochemical characterization of porcine small intestine.

A variety of biotinylated lectins was applied to formalin-fixed intestinal sections from isolator-reared pigs ranging in age from newborn through 12 weeks. Lectin binding to brush borders of villus enterocytes, crypt enterocytes, and dome epithelium, and lectin reactivity within goblet cells and Brunner's glands was semiquantified by microscopy and was used to estimate temporal changes in complex carbohydrates of enteric epithelium. Although variability in binding scores often was observed among pigs of the same age, several general patterns of lectin binding were detected. Dolichos biflorus and Ulex europaeus lectins had increasing binding to brush border membranes as pigs aged. The Dolichos biflorus, however, had decreased binding at the 12-week time point. Neuraminidase-treated Arachis hypogaea and Triticum vulgaris were associated with high mean binding scores at all time points. Canavalia ensiformis bound, with high mean score at all time points, to villus but not to crypt enterocytes. Arachis hypogaea was associated with variable but often high binding scores, regardless of pig age. Succinylated wheat germ agglutinin bound more to crypt than to villus enterocytes. Goblet cells were generally less reactive than were corresponding villi and crypts. Dome epithelium reactivity varied with the lectin used, whereas Brunner's glands reacted with all lectins tested. We conclude that age and regional variations in lectin binding may reflect differences in intestinal function and differentiation. Because complex carbohydrates may act as cell surface receptors for a variety of enteric pathogens, our results indicate that these differences may be partially responsible for age and anatomic differences in susceptibility or resistance to enteric disease.

Aging↗

Hydroxyurea accelerates loss of extrachromosomally amplified genes from tumor cells.

Gene amplification is one mechanism mediating the resistance of tumor cells to antineoplastic agents and the overexpression of a variety of oncogenes in diverse tumor types. There is mounting evidence that acentric extrachromosomal elements such as double minute chromosomes are common intermediates in the amplification process. These acentric structures partition unequally at mitosis and can be lost in the absence of selection. In the present study, we used human and hamster cell lines documented to contain extrachromosomally amplified drug resistance genes to investigate the feasibility of enhancing the loss rate of the extrachromosomally amplified genes to make the cells more sensitive to drug treatment. The results show that treatment of each of these lines with hydroxyurea accelerates the loss of the extrachromosomally amplified drug resistance genes. Loss of these extrachromosomal genes was associated with a corresponding increase in the drug sensitivity in the cases examined. The mechanism of accelerated loss does not appear to involve a differential effect on the replication of extrachromosomal DNA sequences. The results suggest that hydroxyurea treatment may provide a valuable tool for the general accelerated elimination of extrachromosomally amplified genes.

Aspartate Carbamoyltransferase↗

Cotranslocational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum.

Apolipoprotein (apo) B100 is required for the distribution of hepatic triglyceride to peripheral tissues as very-low-density lipoproteins. The translocation of apo B100 into the endoplasmic reticulum (ER) and its subsequent assembly into lipoprotein particles is of particular interest as the protein is both very large (relative molecular mass 512,000) and insoluble in water. It has been proposed that apo B translocation occurs in discrete stages and is completed post-translationally. Several sites of arrest of translocation were reported to be present in apo B15 (the N-terminal 15% of the protein). We have re-examined this question by in vitro translation coupled with translocation into microsomes, and find no evidence for transmembrane segments in truncated apo B proteins. Translocated apo B17 is strongly associated with the membrane of the ER, being only partially releasable with alkaline carbonate, and remaining bound to the microsomes following disruption with saponin. The efficient binding of short segments of apo B, despite the absence of transmembrane domains, suggests that apo B is cotranslationally inserted into the inner leaflet of the ER. This will obviate problems caused by the size and insolubility of apo B100, because the growing hydrophobic protein chains will never exist in a lipid-free form during translocation. From the inner leaflet, apo B in association with membrane-derived lipid can bud into the lumen of the ER to form nascent lipoprotein particles.

Amino Acid Sequence↗

Lipoprotein(a)

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Arteriosclerosis↗