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Biomedical subjects

M Will

Publications and source records attributed to M Will.

At least 19 recordsLinked to original sources

Evaluating medical students on radiology clerkships in a filmless environment: use of an electronic test prepared from PACS and digital teaching collection images.

RATIONALE AND OBJECTIVES: The competency of medical students in radiology clerkships is traditionally evaluated with film images, projected slides of photographed films, or printed reproductions of films. As radiology departments switch to filmless imaging, it seemed appropriate to determine the feasibility of an electronic evaluation prepared directly from digital images. MATERIALS AND METHODS: The image-based portion of a multiple-choice final examination was prepared as a PowerPoint presentation that included images downloaded from the departmental picture archiving and communication system (PACS) or digital teaching collections. The images were downloaded as bitmap files, imported to Adobe Photoshop for image editing, converted to tagged image file format, and finally imported to PowerPoint, where they were combined with text to create 50 questions. A liquid crystal diode projector displayed the questions, with a timer set to advance them automatically. RESULTS: The examination was easy and inexpensive to prepare (no photography costs). In an initial survey of 25 students, 17 (71%) of 24 students rated the resolution of images as excellent and five (21%) as good. No student gave an image a poor rating. Students preferred that images cover at least 40%-50% of the slides, and most approved of a blue background. An original allowance of 30 seconds per slide was reported to be too fast; the interval was increased to 45 seconds. CONCLUSION: An electronic final examination for medical students, prepared with images downloaded from PACS or digital teaching collections, is feasible, easy to prepare, and cost-effective, and it provides an excellent display of test images.

Clinical Clerkship↗

An integrated system for high throughput TaqMan based SNP genotyping.

UNLABELLED: We have developed an integrated laboratory information system that allows the flexible handling of pedigree, phenotype and genotype information. Specifically, it includes client applications for an integrated data import from TaqMan typing files, Mendel checking, data export, handling of pedigree and phenotype information and analysis features. AVAILABILITY: The SQL source code, sources and binaries of the client applications (NT and Windows95/98 platforms) and additional documentation are available at http://www.mucosa.de/.

Clinical Laboratory Information Systems↗

2-acetaminofluorene blocks cell cycle progression after hepatectomy by p21 induction and lack of cyclin E expression.

In the Solt-Faber model DENA and 2-Acetaminofluorene (AAF) treatment combined with hepatectomy induces hepatocellular carcinoma in rats. In this model AAF blocks proliferation of hepatocytes, while oval cells restore liver mass. Here we studied the molecular mechanism involved in blocking AAF-dependent cell cycle progression of hepatocytes. AAF inhibits cell proliferation of hepatocytes shown by the lack of Cyclin E expression before the G1/S phase restriction point. Immunfluorescence studies revealed that Cyclin E positive signals were restricted to oval cells, while hepatocytes remained negative. Additionally, AAF treatment induces strong nuclear p53 expression which is associated with increased p21 mRNA levels. Inhibition of active Cyclin/CdK (cyclin dependent kinase) complexes is reflected in AAF-treated animals by decreased RB expression and phosphorylation. The decrease in RB expression and phosphorylation, which is essential in triggering DNA synthesis and Cyclin A expression, leads to a deficiency in transcriptionally active E2F complex formation after hepatectomy. Thus, two molecular explanations are evident to account for AAF-dependent cell cycle progression of hepatocytes in vivo: first, induction of p53 expression which leads to higher p21 mRNA levels, and second, a lack of Cyclin E expression at the G1/S phase restriction point after hepatectomy.

2-Acetylaminofluorene↗

Contrast-enhanced doppler ultrasound for noninvasive assessment of pulmonary artery pressure during exercise in patients with chronic congestive heart failure.

Pulmonary artery pressure response to exercise was assessed using contrast enhancement of tricuspid regurgitation peak velocities in 19 patients with chronic congestive heart failure. Estimated systolic pulmonary artery pressures correlated closely with invasively measured pressures at rest (r=0.82, p <0.001) and during peak exercise (r=0.86, p <0.001) at a good level of agreement (mean difference 7.3 +/- 12 mm Hg), indicating that this method provides a reliable, noninvasive approach to evaluating functional reserve in patients with chronic congestive heart failure.

Adult↗

The structure of Ro 09-0198 in different environments.

The constitution and configuration of Ro 09-0198 (cinnamycin) have been determined in DMSO. Further investigations in aqueous solution, in SDS micelles and in a lipid bilayer have been done to study the influence of different environments on the conformation of the peptide. It turned out that in spite of the polycyclic structure of the molecule, the conformation is drastically changed going from water to SDS micelles. Ro 09-0198 orients itself in lipid bilayers as expected from its amphiphilic structure. According to a nuclear Overhauser effect spectroscopy experiment under magic angle spinning (MAS) conditions, the molecule is incorporated into the membrane with its hydrophobic part inside the bilayer.

Anti-Bacterial Agents↗

An outbreak of hepatitis A among cancer patients treated with interleukin-2 and lymphokine-activated killer cells.

An outbreak of hepatitis A virus (HAV) infection occurred among cancer patients treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells between July and September 1986 at six different clinical centers. Among 85 patients tested serologically for recent HAV infection, 22 (39%) of 56 susceptible patients developed acute HAV infection. Only exposure to LAK cells cultured in medium containing human serum from two specific manufactured pools was associated with HAV infection. Attack rates were 85% among patients exposed to pool X, 62% in patients exposed to pool Y, and 50% in those exposed to both pools, compared with none among the 24 susceptible persons exposed to other serum pools (P less than .001). The serum used in production of LAK cell medium was obtained from multiple paid donors. Twenty persons donated plasma to both serum pools X and Y. Although none of 12 donors tested had evidence of recent HAV infection, it is likely that an asymptomatic plasma donor viremic for HAV contaminated both serum pools and the LAK cell medium made from it.

Animals↗

Conformational analysis of cyclic peptides in solution.

The strategy and tactics of conformational analysis of cyclic peptides in solution is demonstrated by the example of cyclo(-D-Pro-Phe-Thr-Phe-Trp-Phe-). Spin-locked experiments like rotating frame nuclear Overhauser enhancement spectroscopy (ROESY), ROTO, and TOCSY are successfully applied to assign all proton signals and to obtain distance information. A crude conformational model was built using the nmr data. This starting model was refined by restrained molecular dynamics (MD) calculations using ROE derived distances and fixed bond angles as determined from homo- and heteronuclear coupling constants. To mimic the solvent and to reduce artifacts in an in vacuo calculation the charges of the solvent-exposed NH protons were gradually reduced according to the temperature gradients. The thus obtained "conformation" (mean of a 40 ps MD trajectory) shows very close similarity to x-ray structures in an orthorhombic and in two monoclinic crystal modifications of the same compound. The main difference is the breaking of an intermolecular hydrogen bond of the threonine hydroxyl group on dissolution of the crystal and forming an intramolecular hydrogen bond in solution.

Models, Molecular↗

Application of fourth derivative absorption spectroscopy to protein quantitation during purification.

A method for protein quantitation in the presence of nonprotein cellular components is described. The method is based on measurement of two tryptophan-specific signals in the fourth derivative of the protein's ultraviolet absorption spectrum, a peak at 283 nm and a trough at 288 nm. The amplitude between these two extremes is shown to vary linearly with protein concentration for bovine serum albumin and the outer membrane vesicles of Neissera meningitidis even when these protein solutions are supplemented with enough nucleic acid to completely obscure the parent absorption spectrum of the protein. The utility of this method as an in-process assay during isolation of a protein is demonstrated by comparing estimates of protein content from fourth derivative spectroscopy with those from the Lowry assay for samples at several steps along the isolation pathway for outer membrane vesicles of N. meningitidis. The advantages and limitations of the present method are discussed.

Bacterial Outer Membrane Proteins↗

Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat.

Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed "fetal hydantoin syndrome". The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, we postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, we studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, we examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. We conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

Animals↗

Quality of life.

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Persons with Disabilities↗

Zinc transport proteins in plasma.

1. Both albumin and transferrin have been suggested as carriers of zinc in plasma. Their relative importance in Zn transport was therefore investigated as a preliminary to a study of the rates of passage of Zn through plasma. 2. The apparent log stability constant for Zn binding to human apotransferrin at pH 7.4 was estimated to be approximately 5.9 which is substantially lower than previous reports of 7.0 for the corresponding value for Zn binding to albumin (Giroux & Henkin, 1972). 3. When the relative abilities of human albumin and apotransferrin to compete for Zn with low-molecular-weight chelators were compared at the same relative concentrations of these proteins as are found in plasma, albumin retained substantially more Zn then transferrin. 4. It seems likely that albumin acts as the major transport protein for Zn in plasma of most species, Zn also being present firmly bound to alpha 2-macroglobulin. 5. In porcine plasma or serum however, there were three major Zn-binding proteins, two of which were probably albumin and alpha 2-macroglobulin. The nature of the third component remains unknown but it appeared to have a molecular weight of between 1000000-14000000, it was precipitated by 2.2 M-ammonium sulphate and by 150 g polyethylene glycol/l. 6. There were no significant differences in Zn distribution in plasma of porcine blood obtained from the aorta, the posterior vena cava or from the hepatic portal vein but use of heparin as an anticoagulant altered the normal pattern of distribution of Zn in plasma.

Animals↗

Measurement of zinc flux through plasma in normal and endotoxin-stressed pigs and the effects of Zn supplementation during stress.

1. The rates of transport of zinc through plasma have been investigated in normal and endotoxin-stressed pigs. 2.65Zn added to porcine plasma in vitro rapidly equilibrated with the Zn originally present. 3. 65 Zn bound to albumin and injected intravascularly into pigs rapidly equilibrated with two kinetically distinguishable pools. The first of these pools was mainly associated with the plasma but was significantly larger than the plasma volume and substantially so in Zn-deficient pigs. The second pool appeared to represent a summation of the rapidly-exchangeable Zn within the extravascular tissues. 4. In non-stressed animals, the flux of Zn from the plasma of Zn-deficient pigs was only half that in Zn-supplemented animals. 5. Administration of endotoxin reduced the plasma Zn concentration of Zn-supplemented pigs but not of Zn-deficient animals. The fractional turnover rates of Zn were not altered in eight of the two pools following endotoxin. 6. At 10 h after giving endotoxin neither the Zn content of the two pools nor the flux of Zn through them differed significantly between Zn-deficient and control pigs. 7. Intravascular infusion of Zn at the rate which essentially prevented the usual depression in plasma Zn concentration following endotoxin failed to alleviate the effects of endotoxin on Zn-supplemented pits. 8. The reduction in plasma Zn concentration following endotoxin stress appears to be a normal physiological response which is not indicative of an increased metabolic requirement for Zn.

Animals↗

The assessment of zinc status of an animal from the uptake of 65Zn by the cells of whole blood in vitro.

1. 65Zn uptake by blood cells in vitro has been compared with plasma Zn concentration and plasma alkaline phosphatase (EC 3.1.3.1) activity as indicators of an animal's Zn status. 2. Dietary Zn deficiency, low food intake, reduced dietary protein content and endotoxin administration all reduced plasma Zn concentration in the rat. In each case there was a parallel reduction in plasma alkaline phosphatase activity and an increase in 65Zn uptake in vitro by cells of whole blood. 3. A similar relationship between the three measurements existed in sheep with lowered plasma Zn concentrations whether these were caused by dietary deficiency or by post-surgical stress. 4. 65Zn uptake by cells of whole blood did not differentiate dietary Zn deficiency from the other factors which reduce plasma Zn under 'field' conditions. 5. 65Zn uptake by the cells in whole blood in vitro was three to five times less rapid in blood of ruminant origin than in that from non-ruminants. This difference related to the erythrocytes rather than to the leukocytes or the plasma.

Alkaline Phosphatase↗

Effect of age, weight and adequacy of zinc intake on the balance between alkaline ribonuclease and ribonuclease inhibitor in various tissues of the rat.

1. Deficiency of zinc inhibits growth and also increases the activity of alkaline ribonuclease in certain tissues of the rat (Prasad & Oberleas, 1973). Zn could influence ribonuclease activity by direct effects on the enzyme or its natural inhibitor, or non-specifically as occurs when growth rate is affected by various other factors. These possibilities were studied. 2. Alkaline ribonuclease was shown to be inhibited by Zn in vitro, but the concentrations of Zn required were so high that the enzyme was probably not directly affected by changes in tissue Zn concentration caused by dietary deficiency. 3. At lower concentrations, Zn added in vitro increased the activity of alkaline ribonuclease in tissue homogenates probably by inactivating the inhibitor of the enzyme. 4. Age, weight and particularly food restriction caused tissue-specific alterations of ribonuclease and ribonuclease inhibitor concentrations in liver, kidney, oesophagus, testis and thymus. 5. The ribonuclease activities in liver, kidney and testis of Zn-deficient rats were unaltered in comparison with those of pair-fed rats. In thymus, which decreased in weight in the Zn-deficient animals, there was a concomitant increase in ribonuclease activity, but in oesophagus, the deficiency reduced the activity of ribonuclease. 6. The effects of Zn deficiency upon alkaline ribonuclease and its inhibitor are probably secondary consequences of reductions in food intake or growth.

Age Factors↗