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Biomedical subjects

D J Newman

Publications and source records attributed to D J Newman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Research into the effects of astronaut motion on the spacecraft: a review.

The paper reviews the research that has been undertaken to understand and quantify the disturbance effects of the astronaut's motion inside and outside the spacecraft on the vehicle's attitude and acceleratory environment. In early investigations, the dynamic interaction of astronauts, modeled as point masses, and the spacecraft, modelled as a rigid body, was analyzed. Through ground-based experiments and the modeling of astronaut-induced forces and moments as stochastic processes, it became possible to estimate the magnitude and energy content of the loads produced by the astronaut. The first experiment in space to measure the astronaut-induced disturbances was conducted on the Skylab orbital station. Loads generated while performing routine operations were measured on board the Space Shuttle in 1994 and on the space station Mir in 1996-1997.

Acceleration↗
PubMed2000

How silent is perioperative myocardial ischemia? A hemodynamic, electrocardiographic, and biochemical study in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To analyze the relationship among Holter electrocardiogram (ECG) recordings, hemodynamic measurements indicative of global myocardial oxygen balance, and serum cardiac troponin I concentrations (cTnI) in the early postoperative period after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational study. SETTING: University teaching hospital. PARTICIPANTS: Thirty patients undergoing CABG surgery. INTERVENTIONS: ECG measurements consisted of Holter and standard ECG recordings. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure (SBP, DBP), pulmonary capillary wedge pressure, and cardiac index (CI). Derived indices included tension time index (TTI), rate-pressure product, pressure work index (PWI), and endocardial viability ratio (EVR). Serial measurements of cTnI concentrations were measured postoperatively; the area under the cTnI concentration time curve was calculated for each patient (AUC cTnI). MEASUREMENTS AND MAIN RESULTS: Episodes of myocardial ischemia were associated with small but significant rises in SBP (p = 0.01), DBP (p = 0.001), and TTI (p = 0.005) compared with periods without ischemia in the same patients. Serum cTnI concentrations 24 hours after cardiopulmonary bypass (p = 0.03) and AUCcTnI (p = 0.01) values were greater in patients who developed ECG myocardial ischemia compared with patients who did not. CONCLUSIONS: The small changes in hemodynamics seen, although statistically significant, are unlikely to be the primary cause of the ischemia. They more likely reflect an independent process that causes or occurs as a result of ischemic episodes. Ischemic episodes detected by the Holter monitor are associated with significant release of cardiac troponin from the myocardium.

Adult↗
PubMed2000

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.

Algorithms↗
PubMed2000

Use of COMPARE analysis to discover functional analogues of bleomycin.

Bleomycin was used as the reference compound in a COMPARE analysis to identify extracts in the National Cancer Institute's Natural Products Repository exhibiting cytotoxicity profiles similar to this antitumor agent. One of the extracts so identified was a CH(2)Cl(2)-methanol extract prepared from Gymnosporia trigyna, which effected relaxation of supercoiled pSP64 DNA in the presence of Cu(2+). Bioassay-guided fractionation using DNA strand-scission activity as an end point resulted in the isolation of four active principles. These were identified as syringaldehyde (1), (-)-syringaresinol (2), (+)-catechin (3), and (+)-epicatechin (4). Compounds 1 and 2 represent a new type of DNA strand-scission agent.

Algorithms↗
PubMed2000

Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children.

AIM: To establish a reference range in the paediatric population for the new glomerular filtration rate (GFR) marker, cystatin C, and to compare it with that of creatinine. METHODS: Cystatin C and creatinine were measured by particle enhanced nephelometric immunoassay (PENIA) and fixed interval Jaff¿e methods, respectively, in 291 children aged 1 day to 17 years, including 30 premature infants with gestational ages ranging from 24 to 36 weeks. RESULTS: In the premature infants, concentrations of both cystatin C and creatinine were significantly raised compared with term infants, with cystatin C concentrations being between 1.10 and 2.06 mg/litre and creatinine between 32 and 135 micromol/litre. In premature infants, there was no significant relation between gestational age and cystatin C or creatinine concentration. Creatinine concentrations fell to a nadir at 4 months of age, rising gradually to adult values by about 15-17 years of age, in contrast to cystatin C, which fell to a mean concentration of 0.80 mg/litre by the 1st year of life, and remained constant throughout adulthood up to the age of 50 years. Neither analyte showed any influence of sex. CONCLUSION: The measurement of cystatin C, rather than creatinine, is more practical for monitoring GFR changes in the paediatric population.

Adolescent↗
PubMed2000

Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance.

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 mumol/L, 58-120 ml/min/1.73 m2 and 0.51-0.98 mg/L, respectively. For women, the intervals were 68-98 mumol/L, 60-119 ml/min/1.73 m2 and 0.49-0.94 mg/L; for men, they were 78-123 mumol/L, 57-122 ml/min/1.73 m2 and 0.56-0.98 mg/L. This mean 95% reference interval for cystatin C in all donors under 50 years of age was 0.53-0.92 mg/L; for those over 50 years of age it was 0.58-1.02 mg/L. The small difference between make and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.

Adult↗
PubMed2000

Antineoplastic agents from natural sources: achievements and future directions.

The influence of natural products upon anticancer drug discovery and design cannot be overestimated. Approximately 60% of all drugs now in clinical trials for the multiplicity of cancers are either natural products, compounds derived from natural products, contain pharmacophores derived from active natural products or are 'old drugs in new clothes', where (modified) natural products are attached to targeting systems. This review covers those materials that the authors are aware of as being in clinical trials through early 2000 and demonstrates how, even today, in the presence of massive numbers of agents from combinatorial libraries, the compounds produced by 'Mother Nature' are still in the forefront of cancer chemotherapeutics as sources of active chemotypes.

Animals↗
PubMed2000

A tactile display for international space station (ISS) extravehicular activity (EVA).

BACKGROUND: A tactile display to increase an astronaut's situational awareness during an extravehicular activity (EVA) has been developed and ground tested. The Tactor Locator System (TLS) is a non-intrusive, intuitive display capable of conveying position and velocity information via a vibrotactile stimulus applied to the subject's neck and torso. In the Earth's 1 G environment, perception of position and velocity is determined by the body's individual sensory systems. Under normal sensory conditions, redundant information from these sensory systems provides humans with an accurate sense of their position and motion. However, altered environments, including exposure to weightlessness, can lead to conflicting visual and vestibular cues, resulting in decreased situational awareness. The TLS was designed to provide somatosensory cues to complement the visual system during EVA operations. METHODS: An EVA task was simulated on a computer graphics workstation with a display of the International Space Station (ISS) and a target astronaut at an unknown location. Subjects were required to move about the ISS and acquire the target astronaut using either an auditory cue at the outset, or the TLS. Subjects used a 6 degree of freedom input device to command translational and rotational motion. The TLS was configured to act as a position aid, providing target direction information to the subject through a localized stimulus. RESULTS: Results show that the TLS decreases reaction time (p = 0.001) and movement time (p = 0.001) for simulated subject (astronaut) motion around the ISS. CONCLUSION: The TLS is a useful aid in increasing an astronaut's situational awareness, and warrants further testing to explore other uses, tasks and configurations.

Aerospace Medicine↗
PubMed2000

Adaptive effects of spaceflight as revealed by short-term partial weight suspension.

BACKGROUND: Human performance and adaptation to altered loading levels is investigated. A previous astronaut jumping study demonstrated significantly altered landing performance following spaceflight, complementing reports of postflight postural and gait instabilities. A dynamic model indicated that leg stiffness changes accounted for the kinematic differences due to adaptation in open-loop modulation of leg impedance. Muscular atrophy or altered stretch reflexes and vestibular sensing could not be discounted. HYPOTHESIS: We hypothesize that partial weight unloading can cause modulation of leg impedance and altered jump landing performance similar to longer-term microgravity exposure, while controlling for muscle atrophy and altered graviceptor inputs. Lower-body impedance changes after partial weight unloading support the hypothesis that postflight differences result primarily from modulation of leg impedance due to reduced postural control demands in microgravity. METHODS: Six subjects performed six baseline 30-cm downward jumps from a platform, followed by 10 jumps under 60% body weight unloading (the adaptation sequence), and then six additional jumps under full-body loading (termed "adapted jumps"). Joint and mass center kinematics were compared for the baseline and adapted jump landings. A second order model evaluated changes in vertical leg impedance. RESULTS: Three subjects exhibited significant increased joint angles and rates. Vertical ground reaction forces showed more heavily damped responses after adaptation. Model fits to mass center motion indicated reduced leg stiffness. CONCLUSIONS: Post-adaptation performance is similar to that of four astronaut subjects who demonstrated reduced postflight leg stiffness. The new study strongly suggests adaptive control of lower limb impedance to accommodate altered gravity levels which can be induced by minimal unloading exposure. Partial weight unloading provides a simple, inexpensive analog to spaceflight for certain postural and movement studies.

Adaptation, Physiological↗
PubMed2000

Life in extreme environments: how will humans perform on Mars?

This review of astronaut extravehicular activity (EVA) and the details of American and Soviet/Russian spacesuit design focuses on design recommendations to enhance astronaut safety and effectiveness. Innovative spacesuit design is essential, given the challenges of future exploration-class missions in which astronauts will be called upon to perform increasingly complex and physically demanding tasks in the extreme environments of microgravity and partial gravity.

Extravehicular Activity↗
PubMed1999

Soluble CD8 stabilizes the HLA class I molecule by promoting beta2M exchange: analysis in real-time.

Human soluble CD8 (sCD8) is secreted by activated CD8+/- cytotoxic T lymphocytes (CTLs). The immunological role of sCD8 is poorly defined, however. We have studied the influence of sCD8 on HLA class I interactions by real-time analysis. Using an optical biosensor we demonstrated that the binding of sCD8 to HLA-A2 promotes exchange of beta2-microglobulin (beta2m) in order to stabilize the complex. Kinetic analysis showed that sCD8 significantly increased the affinity (K(A)) of HLA-A2 for immobilized human beta2m; from 1.14 +/- 0.04 x 10(9) M(-1) in its absence, to 2.18 +/- 0.21 x 10(9) M(-1) following preincubation with sCD8. This suggests that the sCD8:HLA class I complex is unlikely to be degraded at the cell surface. Even in the presence of exogenous peptide (HLA-A2 specific or nonspecific), sCD8 has a stabilizing influence on the HLA class I molecule. These findings point to an immunosuppressive role for sCD8, because the binding of sCD8 to HLA class I would block the binding site for CTL-bound CD8 and, therefore, interfere with T cell activation and proliferation. This may have particular significance in pathological situations where elevated levels of sCD8 are found in extracellular fluids, and sCD8 may provide an alternative approach for immunosuppressive therapy.

CD8 Antigens↗
PubMed1999

Heuristic evaluation of a web-based interface for internet telemedicine.

A low-cost usability engineering methodology (heuristic evaluation combined with small-scale expert assessment) is examined in the context of the design and development of a Web-based telemedicine system. Six experts - three human-computer interaction (HCI) experts and three medical-content experts - examined the Spacebridge to Russia Web site for usability. The HCI experts identified 52 interface problems using a set of ten usability criteria or heuristics; these problems ranged in severity from cosmetic to a major failure. The content experts completed a series of six simple tasks while describing their actions. The usage difficulties were related to the HCI problems identified and were primarily characterized by a mismatch of the designer model and the content expert model. This heuristic/usage methodology can provide an incremental benefit in a variety of other design activities. It is suggested herein that the combined heuristic/usage methodology should be included as a standard design component of dynamic telemedicine systems.

Ergonomics↗
PubMed1999

Increased plasma malondialdehyde levels in glomerular disease as determined by a fully validated HPLC method.

BACKGROUND: Reactive oxygen species and particularly free radical induced lipid peroxidative tissue damage have been implicated in the pathogenesis of various renal diseases. Lipid peroxidation is assessed indirectly by the measurement of secondary products, such as malondialdehyde (MDA), using the widely employed thiobarbituric acid reactive substances (TBARS) method. However, this method lacks sensitivity and specificity. We have therefore developed and validated an HPLC (high-performance liquid chromatography) method for measurement of MDA and applied this to a variety of plasma samples in renal patients. METHODS: The optimized method involves antioxidant treatment of the plasma sample, followed by a protein precipitation step using trichloroacetic acid, acid hydrolysis and formation of an MDA thiobarbituric acid complex. The MDA-(TBA)2 adduct is separated from other interfering compounds by C18 reverse-phase HPLC techniques, with visible detection at 532 nm. RESULTS: The assay was linear over the ranges 0.25-1.0 microM MDA and the detection limit was 0.06 microM MDA. Within-run precision was <4.5% and between-run precision was <10.0%. MDA plasma concentrations (mean+/-SD) were higher in ESRF diabetic patients (0.32 +/- 0.14 microM, n=20), non-diabetic ESRF patients (0.32 +/- 0.09 microM, n=20), and CRF patients (0.14 +/- 0.06 microM, n=40) compared to healthy controls (0.11 +/- 0.03 microM, n=40), (P < 0.001, P < 0.001 and P = 0.008). Levels were similar in healthy controls with normal renal function and transplanted patients (0.12 +/- 0.03 microM MDA, n=40), (P=NS). No correlation was observed between MDA and creatinine levels (r2 = 0.05, n=80), which suggests that MDA does not correlate with the degree of renal impairment. We matched CRF patients with glomerular and non-glomerular causes of renal failure for creatinine levels and found that MDA levels were higher in patients with glomerulonephritis (0.16 +/- 0.06 microM) than in those with CRF from non-glomerular causes (0.12 +/- 0.04 microM, P = 0.002). CONCLUSIONS: We have introduced a reliable and sensitive HPLC technique to enhance the specificity of MDA-(TBA)2 measurement, with a significant improvement in HPLC column life. Using this method, picomole quantities of MDA can be detected in plasma. We have shown that MDA levels are significantly raised in patients with CRF due to glomerulonephritis, regardless of serum creatinine, which suggests that there is oxidative injury independent of any possible MDA retention due to renal impairment.

Chromatography, High Pressure Liquid↗
PubMed1999

Memory processes and motor control in extreme environments.

Cognitive-performance and motor-performance activities in multi-task, high-workload environments were assessed during astronaut performance in space flight and in isolation. Data was collected in microgravity on the International Micro-gravity Laboratory (IML) space shuttle mission (STS-42), and the Canadian Astronaut Program Space Unit Life Simulation (CAPSULS) mission offered an ideal opportunity to collect data for individuals in extreme isolation to complement the space flight data using similar hardware, software, and experimental protocols. The mental workload and performance experiment (MWPE) was performed during the IML-1 space flight mission, and the memory processes and motor control (MEMO) experiment was performed during the CAPSULS isolation mission. In both experiments, short-term exhaustive memory and fine motor control associated with human-computer interaction was studied. Memory processes were assessed using a Sternberg-like exhaustive memory search containing 1, 2, 4, or 7 letters. Fine motor control was assessed using velocity-controlled (joystick) and position-controlled (trackball) computer input devices to acquire targets as displayed on a computer screen. Subjects repeated the tasks under two conditions that tested perceptual motor adaptation strategies: 1) During adaptation to the microgravity environment; and 2) While wearing left-right reversing prism goggles during the CAPSULS mission. Both conditions significantly degraded motor performance but not cognitive performance. The data collected during both the MEMO experiment and the MWPE experiments enhance the knowledge base of human interface technology for human performance in extreme environments.

Adaptation, Psychological↗
PubMed1999

A rapid and sensitive automated light scattering immunoassay for serum C-reactive protein and the definition of a reference range in healthy blood donors.

The increasing interest in the measurement of serum C-reactive protein in relation to the risk stratification of patients with chest pain has demonstrated the need for more sensitive routine methods of measurement and an accurate definition of the reference range. We report the determination of a reference range in serum samples from 491 blood donors using a particle enhanced turbidimetric immunoassay that has been modified to offer better imprecision within the reference range. The median values were found to be 2.40 and 2.20 mg/l for males and females, respectively with 95th percentile range of 1.20-5.20 and 0.40-5.40 mg/l, respectively.

Adult↗
PubMed1999

Steroidogenic factor 1-DNA binding: a kinetic analysis using surface plasmon resonance.

Basal expression of the glycoprotein hormone alpha-subunit gene in pituitary gonadotrophs is partially dependent on a gonadotroph specific element (GSE) which binds the nuclear receptor, steroidogenic factor-1 (SF-1). We have used surface plasmon resonance (SPR) to determine the association (kappa ass), dissociation (kappa diss) and affinity (KA) constants of SF-1 binding to immobilized oligonucleotides containing either the GSE consensus motif or a GSE mutant with a 2 bp substitution in the GSE site (GSEMUT). In vitro translated SF-1 protein bound the consensus GSE with a threefold increase in affinity constant (P<0.01) compared with the GSEMUT. This was due primarily to a significant increase (P<0.05) in the kappa ass for SF-1 to the GSE and a slower kappa diss (P<0.05). The binding interaction was specific and could be significantly inhibited (P<0. 001) by either anti-SF-1 antibody or excess non-biotinylated GSE. The addition of 14 bp wild-type flanking sequences significantly reduced the affinity of SF-1 to both the GSE (P<0.05) and the GSEMUT (P<0.01). This was due to a significant (P<0.01) decrease in kappa ass for the wild-type and mutant long oligonucleotides compared with the short GSE. Nuclear extracts from alphaT3-1 gonadotroph cells also bound the GSE and GSEMUT, giving kappa diss values which were two- to threefold slower than those obtained with in vitro translated SF-1. Thus, SPR is a powerful technique for examining kinetic interaction between SF-1 and its binding site, and is able to demonstrate the effects of mutations and flanking sequences on that interaction.

Base Sequence↗