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Biomedical subjects

R Newman

Publications and source records attributed to R Newman.

138 records · Page 8Linked to original sources

EMDep: a web-based system for the deposition and validation of high-resolution electron microscopy macromolecular structural information.

This paper describes the design and implementation of a Web-based deposition system, EMDep, for macro-molecular volumes determined by electron microscopy and deposited at the European Bioinformatics Institute (EBI) for inclusion in the Electron Microscopy Data Base (EMDB). EMDep is a flexible and portable system (http://www.ebi.ac.uk/msd-srv/emdep/) that allows for the acceptance and validation of data, by an interactive depositor-driven operation. The system takes full advantage of the knowledge and expertise of the experimenters, rather than relying on the database curators, for the complete and accurate description of the structural experiment and its results.

Algorithms↗

Selection and properties of a mouse L-cell transformant expressing human transferrin receptor.

Transferrin receptors are expressed in large quantities on tissues with high requirements for iron such as maturing erythroid cells and placenta. In addition, they are found in abundance on proliferating cells from other normal tissues as well as on a variety of tumours. Recent genetic analysis has shown that structural genes for the transferrin receptor, probably transferrin itself and for p97, a melanoma-associated antigen that exhibits primary sequence homology with transferrin and that can bind ferric iron, each map in man to chromosome 3 (refs 9-12). On this basis it has been suggested that there may be a region on chromosome 3 containing genes involved in Fe transport and that rearrangements in this region of chromosome 3 may in some circumstances be associated with malignant transformation. Furthermore, it is unresolved whether all cell types express structurally identical transferrin receptors. To study these problems, and as an initial step towards cloning the transferrin receptor gene, we describe here the derivation of mouse L-cell transformants expressing the human transferrin receptor.

Animals↗

Potent in vitro anticancer activities of ring-expanded ("fat") nucleosides containing the imidazo[4,5-e][1,3]diazepine ring system.

The ring-expanded ("fat") nucleoside, 4,8-diamino-6-imino-6H-1-beta-D-ribofuranosylimidazo[4,5-e][1,3]diazepine (1) and its 2',3',5'-tri-O-benzoyl derivative (2) exhibited potent broad spectrum anticancer activities in vitro against a wide variety of human tumor cell lines. The tribenzoyl derivative 2 was found to be considerably more active than the parent nucleoside 1. Further studies using human prostate cancer cells PC-3 and DU-145 suggest that the treatment of exponentially growing culture cells with 1 and 2 leads to marked loss of cell viability in a dose-dependent manner.

Antineoplastic Agents↗

Rabies: otolaryngologic manifestations.

Rabies is a rare, fatal viral infection, usually transmitted by the bite of an infected animal. Some 30,000 Americans are immunized annually, however, so public health considerations are common. The development of a new vaccine, grown in human diploid cell culture, is discussed. It appears to have high antigenicity with no serious morbidity. A case of a patient with fatal rabies who had fever, delirium, dysphagia, and cervical and pectoral subcutaneous emphysema is presented.

Adolescent↗

Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P < 0.01). Forty-one preeclamptic patients (20 mild, 21 severe) were enrolled. Mean gestational age of severe patients was 32.2 +/- 4.0 and of mild patients was 37.0 +/- 3.5. MAP, SBP, diastolic blood pressure, HR, and SSVRI were higher in the severe group. SVRI, CI, cardiac output, and SI did not differ significantly between groups. Severe preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

Cardiography, Impedance↗

Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase.

Arglabin [1(R),10(S)-epoxy-5(S),5(S),7(S)-guaia-3(4),11(13)-dien-6, 12-olide], a sesquiterpene gamma-lactone is isolated from Artemisia glabella, a species of wormwood endemic to the Karaganda region of Kazakstan. The compound has been modified to render it water-soluble through addition of a dimethylaminohydrochloride group to the C(13) carbohydride moiety to yield Arglabin-DMA. Arglabin-DMA is a registered antitumor substance in the Republic of Kazakstan. Previously, we have shown that this compound prevents protein farnesylation without altering geranylgeranylation. We now report that Arglabin-DMA inhibits the incorporation of [(3)H]farnesylpyrophosphate into human H-ras protein by FTase with an IC(50) of no greater than 25 microM. Kinetic studies show that the phosphorylated form of this compound competitively inhibits the binding of farnesyl diphosphate to FTase. This mechanism of action is different from other reported peptidomimetic FTIs which lower the affinity of ras protein to FTase. Our in vitro studies confirm that Arglabin-DMA inhibits post-translational modification of ras protein in cells. Arglabin-DMA inhibits anchorage-dependent proliferation of NB cells (IC50=10 microg/ml) and inhibits anchorage-independent growth of NB and KNRK cells with about the same IC(50). Soft-agar colony formation assay of H-ras and K-ras transformed cells show IC(50)s to be 2 and 5 microg/ml, respectively. In primary cultures of human tumor cells, Arglabin-DMA inhibits cell proliferation of a variety of tumor types with IC(90)s in the range of 0.85 to 5.0 microg/ml. Because of these pharmacologic properties, we propose that Arglabin-DMA is suitable for the treatment of ras related malignancies.

3T3 Cells↗

A stage-of-change classification system based on actions and beliefs regarding dietary fat and fiber.

PURPOSE: The objectives of this study were to develop a stage-of-change classification system and to determine the degree to which various adult subgroups have adopted the behavioral changes necessary to achieve a low-fat and/or high-fiber diet as recommended by the Dietary Guidelines for Americans. DESIGN: The study used a mail survey randomly sent to 7110 adults. SETTING: The survey was conducted in 11 states and the District of Columbia. SUBJECTS: The random sample included males and females over age 18. Of the eligible respondents, 3198 (51.5%) were included in this analysis, with 2004 and 2066 unambiguously classified into stages of change for fat and fiber, respectively. MEASURES: Stage of change was defined by an algorithm based on self-reported intent and behaviors to limit fat and/or increase fiber. RESULTS: 45% of the respondents were classified as being in action/maintenance for fat and 38% for fiber. Women, older adults, individuals with advanced education, persons with diet-related chronic disease, people with higher levels of relevant nutrition knowledge and attitudes, and persons who indicated that health concerns were a primary influence on their diet were more likely to be in action/maintenance than other respondents. CONCLUSIONS: The algorithm in this study presents a model that more closely reflects the proportions of the adult population that have achieved low-fat diets and classifies a greater proportion in the preparation stage than classification systems in previous studies.

Adult↗

An evaluation of NicCheck I: a dipstick method for analyzing nicotine and its metabolites.

This study examined the reliability of a test strip for assessing urinary nicotine and its metabolites. Urine samples from smokers were tested by two independent raters using the NicCheck I test strips. Each rater compared the test strip color to a five-color chart. Correlations between the rater's codings and between the coding and other measures of nicotine consumption were examined. Significant correlations were found between the two independent ratings of the test strip color and between the codings and other measures of nicotine consumption. This preliminary evaluation suggests that NicCheck I is sensitive to differences in nicotine consumption.

Adult↗

Aztreonam for injection (lyophilized): development of an automated solution batching process utilizing volumetric powder feeders.

As part of a commitment to fully automate the manufacture of a lyophilized dosage form of Azactam (Aztreonam for Injection), an automated solution batching procedure was developed. The lyophilization process requires solution batching of Aztreonam and L-arginine, the two constituents of the product. To avoid preblending of aztreonam and L-arginine prior to dissolution, a batching process was developed which makes use of two separate volumetric powder feeders. In conjunction with a feedback pH control system, these powder feeders provided for (a) a faster batching process, (b) a tight control of solution pH during batching, (c) a failsafe system to prevent operator error and equipment malfunction. Data are presented correlating bulk densities of various powders with feeder output along with solution pH profiles determined using the manual mode and the automated feedback pH control system.

Automation↗