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Biomedical subjects

J E Gray

Publications and source records attributed to J E Gray.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression of a proteasome alpha-type subunit gene during tobacco development and senescence.

Proteasomes degrade specific proteins that have been targeted for proteolysis by ubiquitination. In animals and yeast nuclear-localised proteasomes play a role in regulating the cell cycle, and other developmental processes, via control of the levels of regulatory nuclear proteins such as cyclins and transcription factors. A cDNA, NtPSA1, isolated from tobacco styles was found to have high similarity to human and yeast genes, PRCI_human and PRCI_yeast with 63.4% and 51.6% overall identity respectively. These genes are believed to encode non-catalytic alpha-type subunits of 26S proteasomes and like NtPSA1 have putative nuclear localisation signals. NtPSA1 RNA was found to accumulate to varying levels in different parts of the plant and at different developmental stages. In particular, the level of NtPSA1 RNA was high in young dividing and expanding tissues, and declined during the senescence of both leaves and flowers. These results suggest that a role of proteasomes in plant nuclei may be to regulate developmental events by controlling the levels of regulatory proteins in proliferating and developing tissues, rather than to degrade and recycle proteins during senescence.

Amino Acid Sequence↗
PubMed1998

Variation among neonatal intensive care units in narcotic administration.

OBJECTIVES: To compare rates of narcotic administration for medically treated neonates in different neonatal intensive care units (NICUs) and to compare treated and untreated neonates to assess whether narcotics provided advantages or disadvantages for short-term outcomes, such as cardiovascular stability (ie, blood pressure and heart rate), hyperbilirubinemia, duration of respiratory support, growth, and the incidence of intraventricular hemorrhage. STUDY DESIGN: The medical charts of neonates weighing less than 1500 g, admitted to 6 NICUs (A-F), were abstracted. Neonates who had a chest tube or who had undergone surgery were excluded from the study, leaving the records of 1171 neonates. We modeled outcomes by linear or logistic regression, controlling for birth weight (<750, 750-999, and 1000-1499 g) and illness severity (low, 0-9; medium, 10-19; high, > or =20) using the Score for Neonatal Acute Physiology (SNAP), and adjusted for NICU. RESULTS: Narcotic use varied by birth weight (<750 g, 21%; 750-999 g, 13%; and 1000-1499 g, 8%), illness severity (low, 9%; medium, 19%; and high, 37%), day (1, 11%; 3, 6%; and 14, 2%), and NICU. We restricted analyses to the 1018 neonates who received mechanical ventilation on day 1. Logistic regression, adjusting for birth weight and SNAP, confirmed a 28.6-fold variation in narcotic administration (odds ratios, 4.1-28.6 vs NICU A). Several short-term outcomes also were associated with narcotic use, including more than 33 g of fluid retention on day 3 and a higher direct bilirubin level (6.8 micromol/L higher [0.4 mg/dL higher], P = .03). There were no differences in weight gain at 14 and 28 days or mechanical ventilatory support on days 14 and 28. Narcotic use was not associated with differences in worst blood pressure or heart rate or with increased length of hospital stay. CONCLUSIONS: Our study found a 28.6-fold variation among NICUs in narcotic administration in very low-birth-weight neonates. We were unable to detect any major advantages or disadvantages of narcotic use. We did not assess iatrogenic abstinence syndrome or long-term outcomes. These results indicate the need for randomized trials to rationalize these widely differing practices.

Birth Weight↗
PubMed1998

Advanced multiple beam equalization radiography: receiver operating characteristic comparison with screen-film chest radiography.

OBJECTIVE: To test the hypothesis that the advanced multiple beam equalization radiography (AMBER) imaging system is superior to conventional chest radiography in the demonstration of diffuse infiltrative lung disease, emphysema, pulmonary nodules, calcification within nodules, and mediastinal or hilar masses and lymphadenopathy. MATERIAL AND METHODS: The study involved 115 patients, each of whom underwent chest computed tomography (CT), AMBER, posteroanterior chest radiography, and conventional posteroanterior stereoscopic chest radiography (two films). All radiographs were obtained with the InSight Thoracic Imaging System. Four chest radiologists independently analyzed the 115 AMBER studies, 115 unpaired single conventional radiographs (a single film from a stereoscopic pair), and 115 stereoscopic conventional radiographs (2 films) for the presence of diffuse infiltrative lung disease, emphysema, pulmonary nodules, calcification within nodules, and mediastinal or hilar masses and lymphadenopathy. For each abnormality detected, the radiologists described their level of confidence based on a scale of 1 to 5. The 115 CT examinations were interpreted by consensus among 3 of the chest radiologists. The CT results were considered the standard. Receiver operating characteristic (ROC) techniques were used for statistical analysis. RESULTS: No statistically significant differences were found with ROC techniques between the AMBER system and single or stereoscopic conventional screen-film radiography for the abnormalities studied. CONCLUSION: We noted no clinically significant difference between AMBER and either single or stereoscopic conventional screen-film radiography in this prospective study of 115 patients in which CT (performed within 1 week of both radiographic examinations) was the standard.

Humans↗
PubMed1998

Clinical evaluation of twin screen-film chest radiography: cost effective lung and mediastinal imaging.

OBJECTIVE: A new twin screen-film cassette system optimised for conventional chest radiography was evaluated by four thoracic radiologists. MATERIALS AND METHODS: The twin screen-film cassette system produces two film images, the front film optimised for the mediastinal region of the chest, the rear for the lung region. Image degradation on either screen-film system due to internal photon scatter has been virtually eliminated due to the use of a dividing filter. Fifty patients were included in a trial that resulted in a set of chest images for each patient, taken on the same inspiration, by both the twin screen-film cassette and the conventional system. The resultant fifty sets of images were evaluated by four chest radiologists who scored 12 radiographic features of the chest and patient pathologies present, using a paired difference technique. RESULTS: The image quality of the twin screen-film cassette system was judged to be significantly superior to the conventional screen-film system in nine of the 12 radiographic features scored (P < 0.003). In the three other regions and for the patient pathologies, no significant conclusions were drawn. CONCLUSION: The new twin screen-film system showed improved visualisation of radiographic features, particularly in the mediastinal and retrocardiac lung regions. This new system shows promise in both standard and portable clinical applications.

Cost-Benefit Analysis↗
PubMed1998

Technical aspects of twin screen-film chest radiography: cost effective lung and mediastinal imaging.

OBJECTIVE: To determine the sensitometry and 'cross-talk' of a twin screen-film cassette and to assess its clinical potential. MATERIALS AND METHODS: The twin cassette utilises two sets of screens, divided by filter material, to provide an optimised image of the mediastinum and the lungs. The exposure difference for the two images was measured sensitometrically. The contribution to film density of visible light and K-characteristic radiation, from adjacent screens in the absence of a dividing filter, was investigated. RESULT: Clinical experience indicated that an exposure difference of 3.4 between the front and back screens, was optimal. Visible light and K-characteristic radiation from the front screens, contributed up to 20 and 24% respectively, of the back film exposure and screen absorbed energy respectively. This was reduced to 0 and 6% with the use of the filter. CONCLUSIONS: The twin screen-film cassette provides extended latitude to enable optimal visualisation of the lung and mediastinal regions. Adjacent screen 'cross-talk' has been overcome to allow standard and portable chest applications.

Absorption↗
PubMed1998

Determination of bisnafide, a novel bis-naphthalimide anticancer agent, in human plasma by high-performance liquid chromatography with UV detection.

A simple, specific, and sensitive high-performance liquid chromatographic (HPLC) assay utilizing ultraviolet (UV) detection for the determination of bisnafide in human plasma was developed, validated, and applied to plasma samples from patients undergoing cancer therapy. Plasma samples, containing an internal standard, XE842, were first deproteinized with 2.0 ml acetonitrile, and subsequently, 1.0 ml and pH 9 boric acid-potassium chloride-sodium hydroxide buffer (0.1 M) was added. To this mixture, 9.0 ml of ethyl ether was added then vortex mixed. Following centrifugation, the ether layer was back-extracted into 250 microliters of 0.1 M phosphoric acid, then removed by vacuum aspiration. A portion of the remaining acid layer was directly injected onto the HPLC. Bisnafide was quantified using a Shiseido Capcell Pak C8 HPLC column and ultraviolet detection (274 nm). The lower limit of quantification was 10 ng ml-1 using 1.0 ml plasma. The intraday precision (RSD) ranged from 2.7 to 8.6% over a concentration range of 10-1000 ng ml-1. The interday precision (RSD) ranged from 5.6 to 11.5%. Overall mean accuracy was +/- 5.2%. The drug was stable in frozen heparinized human plasma stored at -20 degrees C for at least 1 year and stable throughout at least two freeze-thaw cycles. This method was successfully utilized for quantifying plasma concentrations needed to study the clinical pharmacokinetics of bisnafide in patients undergoing cancer therapy.

Antineoplastic Agents↗
PubMed1998

A phase I and pharmacologic study of DMP 840 administered by 24-hour infusion.

PURPOSE: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule dependent anti-tumor activity in vitro and in vivo against several tumor cell lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion schedule repeated every three weeks, on the therapeutic efficacy of DMP 840. PATIENTS AND METHODS: Fourteen patients with refractory solid tumor malignancies were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. RESULTS: A combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients. In contrast, all courses at lower dose levels were well tolerated. Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half life (median 39 hours; range 25-86) and that dose-limiting events were significantly related to several indices of systemic DMP 840 exposure (P < 0.01, Wilcoxon Rank Sum test). CONCLUSION: The recommended dose of DMP 840 for further disease oriented evaluations is 40 mg/m2 administered over 24 hours every three weeks. The infusion duration evaluated in this study did not result in a substantial increase in the tolerable dose compared to shorter, less cumbersome schedules.

Adult↗
PubMed1998

Radiation shielding implications of computed tomography scatter exposure to the floor.

This article investigates whether CT scanners used primarily for either head or body work have scattered radiation levels that may impact shielding considerations. Several 35 x 43 cm film cassettes were used to cover the floor area around a General Electric Hi-Speed Advantage CT unit. Regions of maximum exposure were identified (visually with sensitometric confirmation). An ion chamber was used to obtain radiation exposure levels for typical head and body protocols. Greater scattered radiation was found behind the gantry for head scanning (20 vs. 16 microGy for a body scan) while greater scatter was observed in front of the scanner for body scans (46 vs. 31 microGy for the head scan). The resulting annual doses to the floor from typical workloads (assuming 32 cases a day) can be as great as 0.63 Gy for head protocols or 1 Gy from body work. Care may be needed to assure adequate shielding for floor areas near CT scanners specializing in either head or body work. Also, while increased throughput with helical scanners is currently x-ray tube heat limited, shielding plans should allow for enhanced heat capacity (and greater throughput) in future generation scanners.

Health Physics↗
PubMed1998

Intravenous lipid emulsions are the major determinant of coagulase-negative staphylococcal bacteremia in very low birth weight newborns.

BACKGROUND: Intravenous lipid emulsions and the i.v. catheters through which they were administered were the major risk factors for nosocomial coagulase-negative staphylococcal (CONS) bacteremia among newborns in our neonatal intensive care units a decade ago. However, medical practice is changing, and these and other interventions may have different effects in the current setting. OBJECTIVES: We determined the independent risk factors for CONS bacteremia in current very low birth weight newborns after adjusting for severity of underlying illness. METHODS: We surveyed 590 consecutively admitted newborns with birth weights < 1500 g hospitalized in 2 neonatal intensive care units and conducted a case-control study in a sample of 74 cases of CONS bacteremia and 74 pairs of matched controls. Adjusted relative odds of bacteremia were estimated for a number of attributes and therapeutic interventions in 2 time intervals before CONS bacteremia: any time before bacteremia and the week before bacteremia. RESULTS: Using conditional logistic regression to adjust for indicators of severity of illness, two procedures were independently associated with subsequent risk of CONS bacteremia at any time during hospitalization: i.v. lipids, odds ratio (OR) = 9.4 [95% confidence interval (CI) 1.2 to 74.2]; and any surgical or percutaneously placed central venous catheter, OR = 2.0 (95% CI 1.1 to 3.9). Considering only the week immediately preceding bacteremia, the independent risk factors were: mechanical ventilation, OR = 3.2 (95% CI 1.3 to 7.6); and short peripheral venous catheters, OR = 2.6 (95% CI 1.0 to 6.5). CONCLUSIONS: During the last decade exposure to i.v. lipids any time during hospitalization has become an even more important risk factor for CONS bacteremia (OR = 9.4). Of these bacteremias 85% are now attributable to lipid therapy. In contrast the relative importance of intravenous catheters as independent risk factors has declined. Mechanical ventilation in the week before bacteremia has emerged as a risk factor for bacteremia.

Bacteremia↗
PubMed1998

Molecular and enzymatic characterization of three phosphoinositide-specific phospholipase C isoforms from potato.

Many cellular responses to stimulation of cell-surface receptors by extracellular signals are transmitted across the plasma membrane by hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2), which is cleaved into diacylglycerol and inositol-1,4,5-trisphosphate by phosphoinositide-specific phospholipase C (PI-PLC). We present structural, biochemical, and RNA expression data for three distinct PI-PLC isoforms, StPLC1, StPLC2, and StPLC3, which were cloned from a guard cell-enriched tissue preparation of potato (Solanum tuberosum) leaves. All three enzymes contain the catalytic X and Y domains, as well as C2-like domains also present in all PI-PLCs. Analysis of the reaction products obtained from PIP2 hydrolysis unequivocally identified these enzymes as genuine PI-PLC isoforms. Recombinant StPLCs showed an optimal PIP2-hydrolyzing activity at 10 microM Ca2+ and were inhibited by Al3+ in equimolar amounts. In contrast to PI-PLC activity in plant plasma membranes, however, recombinant enzymes could not be activated by Mg2+. All three stplc genes are expressed in various tissues of potato, including leaves, flowers, tubers, and roots, and are affected by drought stress in a gene-specific manner.

Aluminum↗
PubMed1998

Declining severity adjusted mortality: evidence of improving neonatal intensive care.

OBJECTIVES: Declines in neonatal mortality have been attributed to neonatal intensive care. An alternative to the "better care" hypothesis is the "better babies" hypothesis; ie, very low birth weight infants are delivered less ill and therefore have better survival. DESIGN: We ascertained outcomes of all live births <1500 g in two prospective inception cohorts. We estimated mortality risk from birth weight and illness severity on admission and measured therapeutic intensity. We calculated logistic regression models to estimate the changing odds of mortality between cohorts. PATIENTS AND SETTING: Two cohorts in the same two hospitals, 5 years apart (1989-1990 and 1994-1995) (total n = 739). RESULTS: Neonatal intensive care unit mortality declined from 17.1% to 9.5%, and total mortality declined from 31.6% to 18.4%. Cohort 2 had lower risk (higher birth weight, gestational age, and Apgar scores and lower admission illness severity for newborns >/=750 g). Risk-adjusted mortality declined (odds ratio, 0.52; confidence interval, 0.29-0. 96). One third of the decline was attributable to "better babies" and two thirds to "better care." Use of surfactant, mechanical ventilation, and pressors became more aggressive, but decreases in monitoring, procedures, and transfusions resulted in little change in therapeutic intensity. CONCLUSIONS: Mortality decreased nearly 50% for infants <1500 g in 5 years. One third of this decline is attributable to improved condition on admission that reflects improving obstetric and delivery room care. Two thirds of the decline is attributable to more effective newborn intensive care, which was associated with greater aggressiveness of respiratory and cardiovascular treatments. Attribution of improved birth weight specific mortality solely to neonatal intensive care may underestimate the contribution of high-risk obstetric care in providing "better babies."

Hospital Mortality↗
PubMed1998

Detection of small low-contrast objects in mammography: effect of viewbox masking and luminance.

OBJECTIVE: Viewing conditions can affect an observer's performance in object detection. Our objective was to determine the effect of viewbox masking and luminance on the detection of small low-contrast objects revealed by mammography. MATERIALS AND METHODS: Mammographic contrast-detail images having various film densities were viewed on masked and unmasked viewboxes. Similar images with fixed film contrast and density were viewed when luminance ranged from 250 to 8000 nits (1 nit = 1 cd/m2). RESULTS: Detection of small low-contrast objects was significantly easier using a masked viewbox with high luminance that using a regular unmasked viewbox. When a regular viewbox (approximately 3000 nits) was used masking had a more significant effect on films with high optical densities than on films with low optical densities. Brighter, masked viewboxes improved detection on films with higher optical densities. CONCLUSION: Better detection of small low-contrast objects results when mammographic images are masked and viewed on high-luminance viewboxes than when a regular unmasked viewbox is used.

Female↗