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Biomedical subjects

P Todd

Publications and source records attributed to P Todd.

At least 55 records · Page 3Linked to original sources
PubMed1997

Low gravity and inertial effects on the growth of E. coli and B. subtilis in semi-solid media.

BACKGROUND: Several published experimental results have shown that cultures of suspended bacteria exhibit increased growth in the spaceflight environment. HYPOTHESIS AND METHODS: To test whether these differences were due to fluid mechanics and not cellular effects, E. coli and B. subtilis were grown on agar cultures under static, agitated, and rotated conditions in the laboratory, and under low-gravity conditions on four Space Shuttle flights. Growth experiments were terminated with glutaraldehyde, and individual cells were counted after quantitative elution from the agar. RESULTS: The spaceflight results, in conjunction with static, rotation, and agitation experiments indicate that E. coli and B. subtilis cultures on agar, unlike their suspension grown counterparts, do not experience heightened final cell concentration when the inertial environment is changed. CONCLUSIONS: This finding points to fluid dynamics and extracellular transport phenomena and not cellular dynamics as the most likely cause of previously reported increases in bacterial growth in microgravity.

Bacillus subtilis↗
PubMed1996

Sources of selection bias in evaluating social programs: an interpretation of conventional measures and evidence on the effectiveness of matching as a program evaluation method.

This paper decomposes the conventional measure of selection bias in observational studies into three components. The first two components are due to differences in the distributions of characteristics between participant and nonparticipant (comparison) group members: the first arises from differences in the supports, and the second from differences in densities over the region of common support. The third component arises from selection bias precisely defined. Using data from a recent social experiment, we find that the component due to selection bias, precisely defined, is smaller than the first two components. However, selection bias still represents a substantial fraction of the experimental impact estimate. The empirical performance of matching methods of program evaluation is also examined. We find that matching based on the propensity score eliminates some but not all of the measured selection bias, with the remaining bias still a substantial fraction of the estimated impact. We find that the support of the distribution of propensity scores for the comparison group is typically only a small portion of the support for the participant group. For values outside the common support, it is impossible to reliably estimate the effect of program participation using matching methods. If the impact of participation depends on the propensity score, as we find in our data, the failure of the common support condition severely limits matching compared with random assignment as an evaluation estimator.

Bias↗
PubMed1996

Protein crystallization in low gravity by step gradient diffusion method.

Two-step crystallization experiments were conducted in low gravity employing a liquid-liquid diffusion method in an effort to eliminate problems associated with protein crystal growth under the supersaturating conditions required for nucleation. Experiments were performed in diffusion cells formed by the sliding of blocks on orbit. Step gradient diffusion experiments consisted of first exposing protein solutions in diffusion half-wells for brief periods to initiating buffer solutions of high precipitant concentrations to induce nucleation followed by expoure of the same protein solutions to solutions of lower precepitant concentration to promote growth of induced nuclei into crystals. To avoid convective disturbances that occur when solutions of discrepant densities are interfaced at normal gravity, crystallization of hen egg-white lysozyme and rabbit skeletal muscle aldolase by step gradient diffusion was investigated in low gravity on four NASA space shuttle flights. In general, the largest ctystals of both proteins formed at the highest initiating precipitant concentration used, which is consistent with nuclei formation upon brief exposure to high precipitant concentration, and that these nuclei are competent for sustained growth at lower precipitant concentration. The two-step approach dissociates nucleation events from crystal growth allowing parameters affecting nucleation kinetics such as time, precipitant concentration and temperature of nucleation to be varied separately from conditions used for post-nucleation growth.

Animals↗
PubMed1996

Kinetics of nonenzymatic glycation of ribonuclease A leading to advanced glycation end products. Paradoxical inhibition by ribose leads to facile isolation of protein intermediate for rapid post-Amadori studies.

Nonenzymatic glycation (Maillard reaction) of long-lived proteins is a major contributor to the pathology of diabetes and possibly aging and Alzheimer's disease. We report here kinetic studies of the glycation of the model protein ribonuclease A by glucose and ribose leading to the formation of antigenic advanced glycation end products ("AGEs"), detectable by AGE-specific polyclonal antibodies, and pentosidine, an acid-stable fluorescent AGE. As anticipated, the kinetics of glycation by ribose were considerably faster than by glucose, and the rate of AGE formation initially increased with increasing sugar concentrations. However, ribose above 0.15 M appeared to paradoxically slow the kinetics of AGE formation, suggesting ribose inhibits the conversion of "early" Amadori rearrangement products to "late" AGEs and thus favors the accumulation of reactive Amadori intermediates. The facile isolation of such protein intermediates was achieved by an "interrupted glycation" protocol which free and reversibly bound (Schiff base) ribose was removed following a short (24h) initial incubation of 0.5 M ribose at 37 degrees C. The kinetics of buildup of the Amadori intermediates and the kinetics of their post-Amadori conversion to antigenic AGEs were independently studied. A rapid and reversible inhibition of the post-Amadori kinetics by free ribose was verified by direct re-addition of ribose to the isolated, sugar-free intermediate. The pH dependence of the kinetics of antigenic AGE formation from such intermediates was measured and exhibited an unusual bell-shaped profile over the pH range of 5.0-9.5 with a maximum near pH 8.0. Aminoguanidine, a pharmacological AGE inhibitor, was found to moderately or weakly inhibit antigenic AGE formation in such post- Amadori steps. The isolation of the glycated ribonuclease intermediate thus simplifies kinetic and mechanistic studies of AGE formation, permits AGE studies in the absence of complications arising from free or Schiff base bound sugar, and provides a novel methodology for evaluating the mechanism and efficacy of therapeutic agents that may inhibit AGE formation.

Antibodies↗
PubMed1996

Theories and models on the biology of cells in space.

A wide variety of observations on cells in space, admittedly made under constraining and unnatural conditions in many cases, have led to experimental results that were surprising or unexpected. Reproducibility, freedom from artifacts, and plausibility must be considered in all cases, even when results are not surprising. The papers in the symposium on "Theories and Models on the Biology of Cells in Space" are dedicated to the subject of the plausibility of cellular responses to gravity--inertial accelerations between 0 and 9.8 m/s2 and higher. The mechanical phenomena inside the cell, the gravitactic locomotion of single eukaryotic and prokaryotic cells, and the effects of inertial unloading on cellular physiology are addressed in theoretical and experimental studies.

Bacteria↗
PubMed1996

Evaluation of the 2-mm punch biopsy in dermatological diagnosis.

This prospective study was undertaken to determine whether the 2-mm punch biopsy technique yields specimens of sufficient size and quality to allow a reliable histological diagnosis to be made. A histopathological comparison was made between tissue obtained from a 2-mm punch biopsy and a standard ellipse biopsy taken from a wide range of dermatoses and benign and malignant skin tumours. In 79 of the 84 cases studied, the same histopathological diagnosis was reached with the 2-mm punch biopsy and the standard ellipse. Use of the 2-mm punch biopsy technique produces specimens which allow an accurate histological diagnosis to be made in a wide range of dermatological conditions. Skin biopsy techniques should ideally be quick and easy to perform, yielding specimens of high quality and adequate size while leaving the smallest possible tissue defect and a good cosmetic result. The aim of this study was to compare the effectiveness of the 2-mm punch biopsy with that of the standard ellipse biopsy technique in providing skin specimens which permit an accurate pathological diagnosis to be made.

Biopsy↗
PubMed1995

Oral terbinafine and erythema multiforme.

Two patients developed classical erythema multiforme while taking oral terbinafine. A case of Stevens-Johnson syndrome occurring after terbinafine therapy has recently been described, but there have been no published reports of an association with erythema multiforme until now.

Administration, Oral↗
PubMed1995

Ranitidine-induced photosensitivity.

We report the case of a 72-year-old male patient who developed a florid photosensitive eruption while on ranitidine therapy. Ultraviolet A sensitivity was detected by irradiation monochromator testing, suggesting drug-induced photosensitivity. Ranitidine was concluded to be the cause of his photosensitivity since the eruption resolved and the phototest abnormalities returned to normal following cessation of therapy. Similar cases have been reported to the Committee on Safety of Medicines but not published.

Aged↗
PubMed1995

Contact sensitivity to menthol and peppermint in patients with intra-oral symptoms.

We report 12 cases of contact sensitivity to the flavouring agents menthol and peppermint oil in patients presenting with intra-oral symptoms in association with burning mouth syndrome, recurrent oral ulceration or a lichenoid reaction. The patients were referred from the Glasgow Dental Hospital over a 4-year period for assessment of the possible contribution of contact sensitivity to their complaints. 5 patients with burning mouth syndrome demonstrated contact sensitivity to menthol and/or peppermint, with 1 patient sensitive to both agents, 3 positive to menthol only and 1 to peppermint only. 4 cases with recurrent intra-oral ulceration were sensitive to both menthol and peppermint. 3 patients with an oral lichenoid reaction were positive to menthol on patch testing, with 2 also sensitive to peppermint. 9 of the 12 cases demonstrated additional positive patch test results. After a mean follow-up of 32.7 months (range 9-48 months), of the 9 patients that could be contacted, 6 patients described clearance or improvement of their symptoms as a consequence of avoidance of menthol/peppermint.

Adult↗
PubMed1994

Analysis of foreign protein overproduction in recombinant CHO cells. Effect of growth kinetics and cell cycle traverse.

Intracellular foreign protein (beta-galactosidase) expression in recombinant CHO cell lines in continuous culture was analyzed by developing a mathematical model that includes the effects of metabolic burden and cell cycle dependence of intracellular foreign protein expression. This combined growth kinetic and cell cycle model, assuming S- or G1-phase-dependent expression, was stimulated to predict productivity on a single-cell and culture-volume basis in continuous cultures. In the case of S-phase-dependent expression, the intracellular foreign protein level increases monotonically, but in the case of G1-phase-dependent expression it decreases monotonically with increasing dilution rate. Also, the trends of foreign protein concentration in the culture volume differ significantly between S- and G1-dependent expression kinetics. Thus, the cell cycle dependency of foreign protein expression should be included in process optimization concepts and operating strategies of continuous bioreactors.

Animals↗
PubMed1994

Inhalation risk in low-gravity spacecraft.

Inhalation risks on long-duration manned spaced flight include gasses chronically released by outgassing of materials, gasses released during spills, thermodegradation events (including fires) with their attendant particulates, and fire extinguishment. As an example, an event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom was modeled experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity environment was found to impact various stages of event simulation. Critical unknowns were identified, and these include the extent of production of ultrafine particles and polymeric products at the source in low gravity, the transport of ultrafine particles in the spacecraft air quality control system, and the biological response of the lung, including alveolar macrophages, to this inhalation risk in low gravity.

Aerosols↗
PubMed1994

Mechanical analysis of statolith action in roots and rhizoids.

Published observations on the response times following gravistimulation (horizontal positioning) of Chara rhizoids and developing roots of vascular plants with normal and "starchless" amyloplasts were reviewed and compared. Statolith motion was found to be consistent with gravitational sedimentation opposed by elastic deformation of an intracellular material. The time required for a statolith to sediment to equilibrium was calculated on the basis of its buoyant density and compared with observed sedimentation times. In the examples chosen, the response time following gravistimulation (from horizontal positioning to the return of downward growth) could be related to the statolith sedimentation time. Such a relationship implies that the transduction step is rapid in comparison with the perception step following gravistimulation of rhizoids and developing roots.

Biomechanical Phenomena↗
PubMed1994

Cosmic radiation and evolution of life on earth: roles of environment, adaptation and selection.

The role of ionizing radiation in general, and cosmic radiation in particular, in the evolution of organisms on the earth by adaptation and natural selection is considered in a series of questions: (1) Are there times during the evolution of the earth and of life when genetic material could be exposed to heavy ion radiation? (2) Throughout the course of chemical and biological evolution on the earth, what fraction of environmental mutagenesis could be attributable to cosmic and/or solar ionizing radiation? (3) Is ionizing radiation an agent of adaptation or selection, or both? (4) What can the cladistics of the evolution of genetic repair tell us about the global history of genotoxic selection pressures? (5) How much genetic diversity can be attributed to the selection of radiation-damage repair processes?

Animals↗
PubMed1994

Screening for glucose-6-phosphate dehydrogenase deficiency prior to dapsone therapy.

Dapsone is widely used in dermatological practice. The case of a Greek female patient is reported who had a severe, acute, haemolytic episode shortly after commencing dapsone therapy, despite a normal glucose-6-phosphate dehydrogenase (G6PD) screening test. A subsequent quantitative assay revealed reduced levels of G6PD consistent with the heterozygous state. This illustrates that routine screening tests may fail to detect the decreased levels of (G6PD) which occur in female heterozygotes. Since these patients are at risk of severe dapsone-induced haemolysis, the need for quantitative G6PD assays in females from susceptible racial groups is emphasized.

Adolescent↗