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Biomedical subjects

G R Taylor

Publications and source records attributed to G R Taylor.

At least 127 records · Page 7Linked to original sources

Muscarinic cholinergic receptors in a rat phaeochromocytoma cell line.

The high affinity binding of the muscarinic ligand 3H-N-methylscopolamine (3H-NMS) to intact cells of the rat pheochromocytoma cell line PC12 was studied. A single class of saturable binding sites was observed with a density of about 5000 sites per cell, and a pharmacological profile consistent with muscarinic receptors. The inhibition of 3H-NMS binding by the antagonist pirenzepine was of low affinity suggesting PC12 muscarinic receptors may be similar to those found on rat sympathetic nerve terminals.

Animals↗

An audit of therapeutic drug monitoring procedures--use of theophylline assay services.

Monitoring therapy involving drugs exhibiting high intersubject variation and/or narrow therapeutic index has become more generally accepted in hospitals. This paper describes an audit conducted jointly by clinical pharmacists and clinical biochemists into the use and therapeutic value of a drug monitoring service in a general hospital using theophylline as a model. Assay values were categorized as 'subtherapeutic', 'therapeutic' or 'potentially toxic'. The reporting procedures involving the two departments were evaluated along with action taken by the requesting clinicians. The study showed that 60% of the theophylline assay results fell within the therapeutic range at the time of sampling. However only 38% of samples were considered to have been taken under steady state conditions. There was a significant delay in relaying the results to the clinicians. Procedural changes involving sampling times, analytical techniques, recording and conveying results to clinicians and co-operative policies between the departments of pharmacy and clinical chemistry have been implemented as a result of this study.

Adult↗

Herpes simplex virus and Alzheimer's disease: a search for virus DNA by spot hybridisation.

A sensitive hybridisation screening technique (spot hybridisation) was used to search post-mortem brain DNA extracts for herpes simplex I virus sequences in non-neurological controls, Alzheimer's disease cases and Herpes simplex virus infected mice. A reconstruction experiment showed that 0.1 herpes genome equivalents per cell could be detected in 100 micrograms tissue extracts. Although herpes sequences were readily detected in infected mice, none of the human brains examined could be shown to contain such sequences.

Alzheimer Disease↗

Precision cell location and relocation techniques. An application for cell image analysis.

Two methods for precise cell location and relocation were developed at the Cell Image Analysis Laboratory, NASA, to increase the efficiency of the cell image acquisition process. The first method uses a Zeiss Zonax with a 10 micron scanning stage and automatically records cell coordinates on 5.25-inch floppy disks. The second method uses a Digital Positioning Device with a 10 micron scanning stage, and the cell coordinates displayed on light-emitting diodes (LEDs) are recorded manually. Because of its superior speed and automation, the Zonax was selected as the method of choice. By using a Zonax for off-line cell location and another Zonax for on-line cell relocation, more than three times the number of digitized images were collected in ten months than in the previous three years. Other beneficial applications of the cell location and relocation methods were realized in photomicrography, data base verification and cytopathology.

Computers↗

Nuclear segmentation of bronchial epithelial cells by minimax and thresholding techniques. A comparison.

Two nuclear segmentation methods, Baky's minimax algorithm and thresholding, were compared on a sample of 879 atypical bronchial epithelial cells in sputum. Nuclear-cytoplasmic (N/C) ratios for all cells were determined by each segmentation method and compared to a visually determined value. Cells were categorized by atypia class (from metaplastic through malignant), by staining characteristics (orangeophilic and nonorangeophilic) and by method of digitization (either scanning microphotometry or video system). The method of digitization was confounded by subject differences. The results indicated that with most classes of atypia, N/C ratios determined by minimax were closer to the visually derived values than were those of thresholding, particularly with orangeophilic cells. Both methods become progressively less accurate, as compared to the visual procedure, as the degree of atypia increases.

Bronchi↗

Human cellular immune responsiveness following space flight.

Peripheral circulating lymphocytes were separated from astronaut blood samples three times before and two times after the first four US Space Shuttle flights. The ability of the in vitro T lymphocytes to respond to Phytohemagglutinin by blastogenesis was found to be reduced for each crewmember following spaceflight. In addition, the astronauts experienced a postflight increase in neutrophils and a decrease in eosinophils. These postflight changes in leukocytes are shown to increase with subjectively-evaluated increases in the incidence of inflight stress, indicating that stress, and not hypogravity, is likely to be the major effector of these changes.

Aerospace Medicine↗

Classification of bronchial epithelial atypias by the atypia status index.

The atypia status index (ASI) is a categorization method of classifying digitized images of atypical bronchial epithelial cells in sputum. The ASI is defined as a linear composite of features linearly related to atypia stage. Over 200 features were examined for more than 3,000 cells that had been classified by atypia stage (squamous metaplasia, mild, moderate or severe atypia and malignant) and staining characteristic (orangeophilia and nonorangeophilia). We reduced the number of features by using a selection process to minimize redundancy. The feature weights were optimized via a least-squares procedure. The 14 features selected accounted for over 60% of the variation of atypia stage and produced ASI values that were within one atypia stage of the criterion classification for over 90% of the cells. The results are consistent with the hypothesis of a progressive pattern in bronchial epithelial atypia and indicate the feasibility of using image analysis for mass screening of premalignant atypias in sputum from subjects considered to be at high risk for lung cancer.

Adult↗

A comparison of the virucidal properties of chlorine, chlorine dioxide, bromine chloride and iodine.

Chlorine dioxide, bromine chloride and iodine were compared with chlorine as virucidal agents. Under optimal conditions all disinfectants were effective at low concentrations, but each disinfectant responded differently to acidity and alkalinity. Disinfection by chlorine was impaired by the presence of ammonia, but the other disinfectants retained much of their potency. Disinfection of poliovirus by iodine resulted in structural changes in the virions as seen by electron micrroscopy, but the other disinfectants were able to inactivate poliovirus without causing any apparent structural changes.

Bromides↗

Isolation of the thymidylate synthetase gene (TMP1) by complementation in Saccharomyces cerevisiae.

The structural gene (TMP1) for yeast thymidylate synthetase (thymidylate synthase; EC 2.1.1.45) was isolated from a chimeric plasmid bank by genetic complementation in Saccharomyces cerevisiae. Retransformation of the dTMP auxotroph GY712 and a temperature-sensitive mutant (cdc21) with purified plasmid (pTL1) yielded Tmp+ transformants at high frequency. In addition, the plasmid was tested for the ability to complement a bacterial thyA mutant that lacks functional thymidylate synthetase. Although it was not possible to select Thy+ transformants directly, it was found that all pTL1 transformants were phenotypically Thy+ after several generations of growth in nonselective conditions. Thus, yeast thymidylate synthetase is biologically active in Escherichia coli. Thymidylate synthetase was assayed in yeast cell lysates by high-pressure liquid chromatography to monitor the conversion of [6-3H]dUMP to [6-3H]dTMP. In protein extracts from the thymidylate auxotroph (tmp1-6) enzymatic conversion of dUMP to dTMP was barely detectable. Lysates of pTL1 transformants of this strain, however, had thymidylate synthetase activity that was comparable to that of the wild-type strain.

DNA Restriction Enzymes↗

Microflora analysis of a child with severe combined immune deficiency.

An infant with severe combined immune deficiency was delivered by Caesarean section and continuously maintained in an isolator in an effort to restrict microbial contact. However, during the past 5 years the child came in contact with at least 54 different microbial contaminants. His skin autoflora was similar to the reference group of healthy male adults in numbers of different species and the number of viable cells present per square centimeter of surface area. The subject's autoflora differed from the reference group in that significantly fewer anaerobic species were recovered from the patient's mouth and feces. The populations on the skin and in the upper respiratory tract were almost exclusively composed of staphylococci and micrococci, although several species that commonly inhabit these areas were infrequently isolated and failed to colonize. The fecal autoflora was dominated by staphylococci, and bacilli clostridia recovered in typical numbers. Enterobacter agglomerans, not commonly recovered from the reference group, was a frequent inhabitant of the mouth and feces of the child. The fact that this severe combined immune-deficient patient has remained disease free in the presence of this microbial population illustrates the noninvasive nature of the bacteria present, as well as the importance of unaffected components of the child's immune defense mechanism.

Aerobiosis↗

Evaluation of crew skin flora under conditions of a full quarantine lunar-exploration mission.

Crew-members of the Apollo 14 lunar exploration mission underwent a pre-flight seclusion designed to stabilize their health by freeing them from exposure to potentially infectious agents. After the flight, the crew-members were quarantined to protect the biosphere from possible lunar contamination. These isolations, along with the complete isolation of the spaceflight itself, provided the opportunity for a skin flora survey which included the sampling of seven sites at five different times. Quantification and identification of all aerobic and anaerobic bacteria from each site were performed. The results indicated that the pre-flight quarantine measures resulted in a decrease in total numbers of isolates as well as a decrease in the anaerobes. This was followed by a continued decrease throughout the flight with a return to the pre-flight norm within 16 days after the flight. The quantitative load of aerobic bacteria increased during the flight, due largely to an increase in coryneforms and micrococcaceae. The quantitative load of anaerobic bacteria decreased before and during the flight. No instance of microbial shock or intercrew transfer of micro-organisms was demonstrated. These findings indicate that alterations in the skin flora do not pose any unusual problem during short duration space flights. Further, there are no indications that problems will arise on longer missions.

Bacteria↗

Medically important micro-organisms recovered from Apollo-Soyuz Test Project (ASTP) crew members.

The possibility of significant alterations in the microbial populations inhabiting the integument and upper respiratory tract of space flight crew members has been proposed by various authors. The Apollo-Soyuz Test Project (ASTP), a unique space flight in which two teams of crew members from different geographical areas joined in space, presented an unusual opportunity to evaluate in-flight cross-contamination and other anomalous behavior of the microbial populations. Accordingly, the medically important microbes recovered from the five (3 USA and 2 USSR) ASTP crew members before and after flight were evaluated in relation to specific theoretical alterations. The phenomenon of "simplification", in which the number of different types of species is reduced during spaceflight, did not occur within the population of medically important micro-organisms. Spontaneous post-flight illness due to infectious agents ("Microbial Shock") was also absent. Intracrew transfer of pathogens was established, but intercrew transfer was absent. Dysbacteriosis, in which sampled areas are flooded with unusually large numbers of a single type of micro-organism, was not demonstrated although there was a significant increase in the incidence of gram-negative rods in the oral cavities of the two cosmonauts. The importance of all of these and other observations of the medically important micro-organisms recovered from ASTP crew members are explored with respect to past and future space flights.

Aerospace Medicine↗

Growth-rate periodicity of Streptomyces levoris during space flight.

Streptomyces levoris Kras was used is an experimental test micro-organism during the Apollo Soyuz Test Project to study alternating vegetative mycelial and spore ring periodicity during space flight. Four cultures were launched in each of the spacecrafts (Apollo and Soyuz). During the joint space-flight activities, two cultures from each spacecraft were exchanged. Selected duplicate cultures were maintained as controls in both the USA and the USSR. Spore ring morphology was periodically documented by photographing the specimens at approximately 12-hr intervals during the pre-, in-, and post-flight periods of the experiment. A decreased growth-rate periodicity in all but one of the eight space-flight cultures was in part attributed to the reduced temperature in the spacecraft. One of the eight cultures grew at a faster rate in the reduced temperature environment of Apollo than did the ground controls. Three of the space-flight cultures developed double spore rings during the immediate post-flight period. This anomaly was attributed to re-entry into the earth's gravity. The absence of spores in portions of one ring formed during space flight may have been caused by nutritional defects or media abnormality. Extensive studies will be required to elucidate the cause of this detect with certainty. There was no visible evidence of wedges in the cultures which would suggest naturally occurring or radiation-induced mutagenic alteration during space flight.

Circadian Rhythm↗

Autoflora in the upper respiratory tract of Apollo astronauts.

The typical microbial inhabitants of the oral and nasal cavities of Apollo astronauts were identified before space flight and generally found to be similar to those previously reported for healthy male adults. Additional analyses of samples collected immediately after return of the Apollo 13, 14, 15, and 16 crew members to earth were performed to evaluate the effects of space travel on the microbial bioburden of the upper respiratory tract. In-flight cross-contamination and buildup of pathogens such as Staphylococcus aureus were noted, although significant increases in nonpathogenic species were absent. Other proposed alterations, such as dysbacteriosis (flooding of the mouth with a single species) and simplification of the autoflora, did not occur. Generally, the incidence and quantitation of each species after flight was within the preflight range, although the number of viable Haemophilus cells recovered from the mouth decreased significantly after space flight. Except for those minor alterations listed above, the aerobic and anaerobic bacterial components of the upper respiratory autoflora of Apollo astronauts was found to be stable after space flight of up to 295 h.

Adult↗

Physical dosimetric evaluations in the Apollo 16 microbial response experiment.

Nine biological species, including viruses, bacteria, fungi, and nematodes, were exposed to various combinations of space vacuum, galactic radiation, and solar UV light during the Apollo 16 space flight. No major changes in number of surviving cells occurred, permitting detailed genetic and somatic studies of returned test subjects. To enable dose-response studies, solar UV was employed as a mutagenic source with cells exposed to full sunlight or to components of the UV spectrum at peak wavelengths of 254, 280, and 300 nanometers over a range of energy levels. Proper in-flight UV irradiation monitoring required the development of a potassium ferrioxalate actinometer and an anaerobic photographic emulsion dosimeter which were tested for the first time in space. Studies of the mutagenic activity of cosmic-ray particulate radiation environment required measurement of its components with several lithium fluoride thermoluminescent dosimeters and a package of passive nuclear-track detectors capable of recording high-energy multicharge particles. These detectors included cellulose nitrate, Lexan, Ilford G5, and silver chloride crystals. The nuclear track detectors measured the incident heavy particles with the recorded spherical fluences with LET350,H2O>100 keV x micrometers-1 to be 19.3 +/- 1.8 particles cm-2. This value was found to be lower than that recorded by detectors located in the Biostack and the passive personnel dosimeters worn by the astronauts, suggesting a somewhat greater average shielding.

Animals↗

Effects of solar ultraviolet radiations on Bacillus subtilis spores and T7 bacteriophage.

Spores of Bacillus subtilis HA 101 and the DNA polymerase I-defective mutant HA 101 (59) F were exposed to selected wavelengths of solar ultraviolet light and space vacuum during the return of Apollo 16. In addition, coliphage T7 suspensions were exposed to solar ultraviolet radiation as part of the Microbial Response to Space Environment Experiment. Optical filters were employed to provide different energy levels at wavelengths 254 nm and 280 nm. Dose-response curves for lethal and mutagenic effects were compared with ground-based data. A close parallel was observed between the results of solar radiation and ground tests with spores of the two strains. However, significantly greater inactivation of T7 bacteriophage was observed after exposure to solar ultraviolet radiation.

Bacillus subtilis↗