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Biomedical subjects

N Richardson

Publications and source records attributed to N Richardson.

At least 19 recordsLinked to original sources

Production, in vitro characterisation, in vivo clearance, and tissue localisation of recombinant barramundi (Lates calcarifer) insulin-like growth factor II.

Recombinant barramundi insulin-like growth-factor-II (bIGF-II) has been produced in Escherichia coli after modification of an expression plasmid that coded for a chicken IGF-II fusion protein. The bIGF-II fusion protein, deposited in bacterial inclusion bodies, was dissolved under reducing conditions, desalted, and refolded. The protein was then released from the fusion protein by cleavage with subtilisin BPN'. Finally the protein was purified to homogeneity with a number of HPLC steps. In vitro analysis of recombinant bIGF-II demonstrated decreased potency in stimulating protein synthesis when compared to human and barramundi IGF-I (bIGF-I). The in vivo distribution of radiolabeled bIGF-II and bIGF-I in the circulation and tissue uptake of radiolabeled bIGF-II was also compared in juvenile barramundi (Lates calcarifer). Analysis of trichloroacetic acid-precipitable radioactivity in sequential samples following bolus injection of radiolabeled IGFs revealed that bIGF-II was degraded faster than bIGF-I. Moreover, neutral gel chromatography of these samples suggested this difference may be due to reduced affinity of bIGF-II, compared to blGF-I, for the IGF-binding proteins (IGFBPs) present in the barramundi circulation. Based on these results, it would appear that elements important in the function of IGFs have been well conserved during vertebrate evolution. However, to clearly define the IGF system in fish it will be necessary to characterise the IGFBPs present and to determine how they influence the biological actions of native IGFs.

Amino Acid Sequence↗

Broad specificity alkaline proteases efficiently reduce the visual scaling associated with soap-induced xerosis.

In xerotic skin, the proteolysis of desmosomes is reduced leading to the accumulation of corneocytes on the surface of the skin. The effect of proteases applied topically to soap-induced xerotic skin was evaluated using a five-point visual scale. The visual scaling associated with soap-induced xerosis could be ameliorated by the topical application of exogenous protease. Bovine pancreatic chymotrypsin, papain, and a bacterial protease from Bacillus licheniformis were all capable of facilitating the reduction in visual scaling in a short time. Alcalase and Optimase, both broad specificity alkaline bacterial proteases, were the most weight-efficient at delivering this clinical effect. The reduction in scaling could be achieved either by occluded application of an aqueous enzyme solution or by a two-step unoccluded application first of an aqueous enzyme solution followed by a commercial moisturizer. Morphological and immunological analysis of bacterial enzyme-treated skin revealed that topically applied protease specifically induced the degradation of the desmosomes thereby promoting desquamation. These results indicate that topical application of protease can significantly and rapidly reduce the visual scaling associated with soap-induced xerosis by promoting desmosome degradation within the corneocyte clumps.

Administration, Topical↗

Haloperidol blood levels in acute mania with psychosis.

In this study, the authors examined the relationship between steady-state haloperidol blood levels and clinical response in patients with acute psychotic mania. Fifty-four inpatients with acute mania were randomly assigned to receive either haloperidol 25 mg/day or haloperidol 5 mg/day. Each subject also received a concomitant medication: lorazepam 4 mg/day, lithium, or placebo. The relationship between steady-state haloperidol blood levels and clinical improvement was studied using analysis of covariance. There was wide interindividual variation in the haloperidol blood level-dose ratio. Haloperidol blood levels (log-transformed) were found to significantly correlate with clinical response in acute mania. Low-dose haloperidol with concomitant lithium may produce an optimal response in acute mania. Haloperidol blood levels may be clinically useful in identifying patients who are nonresponsive because of low drug levels and, hence, in enhancing optimal haloperidol dosing for acute mania with psychosis.

Adult↗

Comparison of recombinant barramundi and human insulin-like growth factor (IGF)-I in juvenile barramundi (Lates calcarifer): in vivo metabolic effects, association with circulating IGF-binding proteins, and tissue localisation.

The in vivo actions of human and fish insulin-like growth factor (IGF)-I have been compared to extend the understanding of the metabolism of IGFs in fish and to identify potential differences in their actions. The effects of acute administration of these proteins on the incorporation of glucose into muscle glycogen and leucine into liver protein in juvenile barramundi were investigated. In these in vivo metabolic assays, both baramundi IGF-I (bIGF-I) and human IGF-I (hIGF-I) increase the incorporation of D-[14C]glucose into muscle glycogen and [14C]leucine into liver protein. The distribution of radio-labeled human and barramundi IGF-I in the circulation and their uptake by tissue was also compared in juvenile barramundi (Lates calcarifer). Analysis of trichloroacetic acid-precipitable radioactivity in sequential samples following bolus injection of radiolabeled IGFs revealed that hIGF-I was degraded faster than bIGF-I. Neutral gel chromatography of these samples suggested that this difference is due to reduced affinity of hIGF-I, compared to bIGF-I, for the IGF-binding proteins (IGFBPs) present in the barramundi. Tissue uptake of [125I]-labeled hIGF-I and bIGF-I was similar except that [ 125I]bIGF-I uptake by the kidney exceeded that of hIGF-I. It is suggested that while some of the in vivo actions of IGFs in fish are conserved, functional differences between mammalian and teleostean IGFs exist, particularly with respect to their interactions with fish IGFBPs.

Animals↗

Benchmark testing the Digital Imaging Network-Picture Archiving and Communications System proposal of the Department of Defense.

The Department of Defense issued a Request for Proposal (RFP) for its next generation Picture Archiving and Communications System in January of 1997. The RFP was titled Digital Imaging Network-Picture Archiving and Communications System (DIN-PACS). Benchmark testing of the proposed vendors' systems occurred during the summer of 1997. This article highlights the methods for test material and test system organization, the major areas tested, and conduct of actual testing. Department of Defense and contract personnel wrote test procedures for benchmark testing based on the important features of the DIN-PACS Request for Proposal. Identical testing was performed with each vendor's system. The Digital Imaging and Communications in Medicine (DICOM) standard images used for the Benchmark Testing included all modalities. The images were verified as being DICOM standard compliant by the Mallinckrodt Institute of Radiology, Electronic Radiology Laboratory. The Johns Hopkins University Applied Physics Laboratory prepared the Unix-based server for the DICOM images and operated it during testing. The server was loaded with the images and shipped to each vendor's facility for on-site testing. The Defense Supply Center, Philadelphia (DSCP), the Department of Defense agency managing the DIN-PACS contract, provided representatives at each vendor site to ensure all tests were performed equitably and without bias. Each vendor's system was evaluated in the following nine major areas: DICOM Compliance; System Storage and Archive of Images; Network Performance; Workstation Performance; Radiology Information System Performance; Composite Health Care System/Health Level 7 communications standard Interface Performance; Teleradiology Performance; Quality Control; and Failover Functionality. These major sections were subdivided into workable test procedures and were then scored. A combined score for each section was compiled from this data. The names of the involved vendors and the scoring for each is contract sensitive and therefore can not be discussed. All of the vendors that underwent the benchmark testing did well. There was no one vendor that was markedly superior or inferior. There was a typical bell shaped curve of abilities. Each vendor had their own strong points and weaknesses. A standardized benchmark protocol and testing system for PACS architectures would be of great value to all agencies planning to purchase a PACS. This added information would assure the purchased system meets the needed functional requirements as outlined by the purchasers PACS Request for Proposal.

Benchmarking↗

RNA editing.

Explore the source record for details and available documents.

APOBEC-1 Deaminase↗

Secondary structure for the apolipoprotein B mRNA editing site. Au-binding proteins interact with a stem loop.

The C to U editing of apolipoprotein B (apoB) mRNA converts a glutamine codon in apoB100 mRNA into a stop translation codon thereby generating apoB48. The catalytic subunit of the editing enzyme, APOBEC-1, is an RNA-binding cytidine deaminase that requires auxiliary factors for the editing of apoB mRNA. Computer modeling and ribonuclease probing of the wild-type and mutant apoB RNA substrates reveal a stem loop at the editing site. This structure incorporates the essential sequence motifs required for editing. The localization of the edited cytidine within the loop suggests how it could be presented to the active site of APOBEC-1 for deamination. We have identified 43/45 kDa proteins from chick enterocytes and show evidence for their involvement in auxiliary editing activity. p43/45 demonstrates preferential binding to AU-rich RNA and to the Caauuug motif that forms the loop and proximal stem of the apoB mRNA.

APOBEC-1 Deaminase↗

Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition.

ApoB RNA-editing enzyme (APOBEC-1) is a cytidine deaminase. Molecular modeling and mutagenesis show that APOBEC-1 is related in quaternary and tertiary structure to Escherichia coli cytidine deaminase (ECCDA). Both enzymes form a homodimer with composite active sites constructed with contributions from each monomer. Significant gaps are present in the APOBEC-1 sequence, compared to ECCDA. The combined mass of the gaps (10 kDa) matches that for the minimal RNA substrate. Their location in ECCDA suggests how APOBEC-1 can be reshaped to accommodate an RNA substrate. In this model, the asymmetrical binding to one active site of a downstream U (equivalent to the deamination product) helps target the other active site for deamination of the upstream C substrate.

APOBEC-1 Deaminase↗

Organization, sequence, and expression of the gene encoding IGFII from barramundi (Teleosteii; Lates calcarifer).

We have characterized the gene encoding IGFII from the teleost fish species barramundi, Lates calcarifer. The barramundi gene spans 5.5 kb of DNA and comprises four exons and three introns. The barramundi and salmon IGFII genes share > 85% sequence similarity across all the exons and also share some regions of high sequence identity within the promoter regions and the introns. The mature barramundi IGFII peptide comprises 70 amino acid residues and shares 84 and 96% similarity with salmonid and seabream IGFII, respectively, with the majority of replacements located in regions cleaved from the mature peptide. IGFII mRNA transcripts were detected in liver, muscle, intestine, gill, heart, and brain from juvenile barramundi. This distribution mirrors that seen in the rainbow trout and seabream and extends the tissue types which synthesize IGFII in fish to include the intestine.

Amino Acid Sequence↗

Iron-based second-sphere contrast agents for magnetic resonance imaging: development of a model system and evaluation of iron (III) tris (tironate) complex in rats.

RATIONALE AND OBJECTIVES: Iron(III) complexes have been developed as magnetic resonance (MR) contrast agents based on the use of ligands capable of providing coordinative saturation at iron and allowing the second-sphere hydrogen bonding of water molecules. METHODS: Studies of solution-phase binding of a probe ion to a diamagnetic metal catecholate complex and molecular orbital calculations were performed. R1 values were determined. Toxicity studies of iron(III) tris(tironate) were conducted with rats. Excretion studies were performed by analysis of urine samples. MR measurements were made. RESULTS: Second-sphere coordination of a probe ion to a metal catecholate complex occurred in solution. Molecular orbital calculations suggested flexibility in design. Iron(III) tris (catecholate) complexes were shown to have high R1 values. Images of the kidneys and liver showed dose-dependent enhancement in T1-weighted images. The onset of toxicity was at approximately 0.30 mmol/kg. Urine analysis indicated essentially complete clearance (0.1-0.2 mmol/kg) within 24-48 hours. CONCLUSION: Interactions between water molecules and basic sites within a paramagnetic metal-ligand complex allow for application of suitable complexes as T1 agents.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Total antioxidant capacity and lipid peroxidation during liver transplantation.

1. We assessed plasma total antioxidant capacity using enhanced chemiluminescence and plasma lipid peroxides in eight patients undergoing orthotopic liver transplantation and 26 healthy control subjects. 2. The antioxidant capacity of plasma decreased significantly on reperfusion of the donor liver (P < 0.05) during liver transplantation, although levels were not lower in patients than in control subjects. 3. Pre-reperfusion antioxidant capacity correlated negatively with the concentration of lipid peroxidation products appearing in the plasma by the end of the transplant (P < 0.02), but did not correlate with vitamin A or E concentrations. 4. This study provides evidence of oxidant stress during liver transplantation, as shown by antioxidant utilization associated with increased lipid peroxidation.

Adult↗

The effect of anticoagulant choice on apparent total antioxidant capacity using three different methods.

We assessed total antioxidant capacity using three different methods, in plasma samples treated with either EDTA or heparin as anticoagulant, from 26 healthy subjects. Total antioxidant capacity was determined using an oxygen electrode (as the total peroxyl radical-trapping antioxidant parameter), by enhanced chemiluminescence, and by measurement of the antioxidant-mediated quenching of the absorbance of a radical cation. The choice of anticoagulant had a profound effect on antioxidant capacity with heparinized plasma giving consistently higher values than plasma anticoagulated with EDTA. Using the oxygen electrode the mean value was 786.5 +/- 171.5 mumol/L (heparin) compared to 681.4 +/- 160.4 mumol/L (EDTA, P < 0.01). The chemiluminescence technique gave a mean antioxidant capacity of 915.6 +/- 214.1 mumol/L in heparin samples and 714.4 +/- 195.4 mumol/L in EDTA samples (P < 0.0001). The absorbance quenching technique gave a mean value of 867.0 +/- 199.2 mumol/L (heparin) and 675.5 +/- 245.4 mumol/L (EDTA, P < 0.001). All methods tested showed comparable results for EDTA plasma, but the chemiluminescence technique gave higher apparent antioxidant capacity than either of the two techniques when heparin plasma was used. We suggest that either heparin is interacting to enhance antioxidant protection perhaps through release of superoxide dismutase, or the chelation of metal ions by EDTA is limiting the activity of antioxidant metalloenzymes. Consistency in the choice of anticoagulant is clearly extremely important.

Adult↗

Vigilance as a table of numbers.

Data from vigilance experiments have structure. Its bases include 1/12 and multiples thereof, single-digit fractions, and 1/e. Continuing previous research, a table of e-based ratios (e-BR) was developed. Data from 9 published experiments with regular and irregular signals (RS-IS) and from 9 with extraverted and introverted subjects (E-I) were re-analyzed. Significant numerical correlations were obtained, some concerning effects originally reported as nonsignificant. Detection (D) means all categories ("levels" of both factors) were linearly related, with p(D) approximately mean(5/8 + y/9) and p < .01. Cross-factor averaged mean products of ratio D for each time period also showed convergence (p < .01). The over-all mean and stability ratio of detections (SR[D], i.e., D for final time period/D for initial time period, gave the scaling effect 8 square root of 1/24:24 square root of 1/24. Response-time means and standard deviations for different groups in Mackie, Wylie, and Smith's 1994 sonar experiments were related by the derivatives of [1 - 1/e] included in the new table (p = .002). Although by no means specific to vigilance (or psychophysics), the numeric factor still seems relevant to research.

Arousal↗

A statewide public and professional education program on fragile X syndrome.

Fragile X syndrome is reported to be the most common inherited cause of mental retardation known, but the majority of affected individuals are as yet undiagnosed. The project described in this paper was developed to increase the public and professional awareness of fragile X syndrome in the state of New Jersey. As a result there were increased efforts at diagnostic screening, provision of client and family support services, and prevention. This educational program proved to be a cost-effective method for increasing community awareness of a genetic disease on a statewide level.

Adolescent↗

Randomized controlled study of a retiree health promotion program. The Bank of American Study.

The initial results of a 12-month controlled trial of a health promotion program in 5686 Bank of America retirees, randomized into full program, questionnaire only, and insurance claims only groups, were analyzed to determine whether the health promotion program was effective. Comparisons were between program and questionnaire only groups for self-reported health habit changes, health risk scores, medical care utilization, and days confined to home, and between all groups for insurance claims data. The intervention, or full program, included health habit questionnaires administered every 6 months, individualized time-oriented health risk appraisals, personal recommendation letters, self-management materials, and a health promotion book. Twelve-month changes in health habits, health status, and economic variables favored the full program group in 31 of 32 comparisons and were statistically significant at the .05 level in two-tailed tests in 19 comparisons and at the .01 level in two-tailed tests in 13 comparisons. Over 12 months, overall computed health risk scores decreased by 4.3% in the full program experimental group and increased by 7.2% in the questionnaire only control group. Total direct and indirect costs decreased by 11% in the experimental group and increased by 6.3% in the questionnaire only control group. Analysis of claims data confirmed these trends. A low-cost health promotion program for retirees was effective in changing health behaviors and has potential to decrease health care utilization.

Aged↗

Vigilance ratios implicate biological rhythms.

Vigilance research has been focused on differences, yet ratios might have intrinsic, numerical significance. Reanalysis of data from Watkins' 1963 psychophysical experiment and 49 vigilance reports showed that individual and group ratios, including errors or misses: detections, were related to roots (particularly of base 1/12 and multiples), powers, e-base ratios (EBR), and fractions. Examples are given from well-known experiments of remarkably exact relationships between conditions, time periods, etc. It is suggested that these phenomena are the product of biological rhythms. Theoretical implications are briefly discussed and the advantages of ratio analysis noted, as when this method proved that criterion beta changes, given as nonsignificant, formed part of an ordered set. In a real-world application, the frequency of lane-drifts in O'Hanlon and Kelly's 1977 report is shown to follow a mathematical pattern.

Arousal↗