PCR for the detection of genital human papillomavirus infection: a mixed blessing.
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Female↗
Biomedical subjects
J R Ellis
Publications and source records attributed to J R Ellis.
The relationship between visual stimulation, behaviour and continuous release of protein in the substantia nigra.
In the substantia nigra, a protein (acetylcholinesterase) is secreted from the dendrites of dopaminergic pars compacta neurons, in a noncholinergic capacity. This non-classical phenomenon could be influenced by sensory stimulation: the effect of light flashing was investigated on the 'on-line' release of acetylcholinesterase and concomitant behaviour in the guinea-pig. The stimulus induced an increase in release of the protein and the appearance of chewing movements. Similarly, chewing could also be elicited by direct local application of exogenous acetylcholinesterase. The results suggest that visual stimulation causes release of AChE, which in turn facilitates movement. Therefore secretion of this protein within the substantia nigra might form an important intermediary step in visuo-motor interactions.
Acetylcholinesterase↗
A diet high in fat stimulates adipocyte proliferation in older (22 month) rats.
The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.
Adipose Tissue↗
Theoretical considerations for improving tumour targeting.
To determine the relative importance of factors influencing tumour uptake of antibodies, we used a mathematical model to simulate intravenous injection of substances of varying molecular sizes and tumour-binding affinities at several dose levels. The FACSIMILE program was used to simulate the time course of tumour uptake of the tumour-binding substance by calculating the instantaneous tumour content (TC) and tumour:background uptake ratios (UR). Relative total doses to tumour and normal tissue were calculated by integration of TC/time curves. The model was used to make theoretical predictions on the effects of altering different parameters. The size of the injected dose in relation to the number of tumour receptors was crucial:if too low, uptake could not be improved by manipulating other variables, and if too high, the UR for large binding molecules was reduced. Using the standard scanning dose of labelled antibody, absolute numbers of labelled molecules binding to tumour could be increased by injection of a large excess of unlabelled molecules. Given an adequate dose, peak tumour content increased with increasing affinity up to receptor saturation. The peak uptake ratio rose progressively with affinity for a small ligand, but reached a relatively low plateau for antibody due to constant high background levels. At low doses such as those currently administered for diagnostic scanning with antibody, no effect of increasing affinity was predicted.
Antibodies, Monoclonal↗
Effect of dose, molecular size, affinity, and protein binding on tumor uptake of antibody or ligand: a biomathematical model.
A mathematical model has been developed to determine the best approach to improving tumor targeting with antibody. The amount of antibody in the tumor (tumor content) and the tumor:normal tissue antibody concentration ratio (uptake ratio) were calculated over 12 days from injection, using the computer program FACSIMILE to solve the stiff nonlinear differential equations describing the system. Results indicate that success requires an optimal combination of dose, size, and binding affinity of antibody. Increasing the dose to 100 times that presently used for scanning increased both the percentage of injected antibody in the tumor and the uptake ratio by up to 2 orders of magnitude to maximal values determined by affinity. This result could be achieved by coinjecting unlabeled antibody. Increasing affinity from Keq = 10(9) to 10(13)M-1 increased the uptake ratio from 5 to 100 for whole antibody and to 550 for a small ligand, at the calculated optimal dose, but had no effect at the current scanning dose. With decreasing molecular size at average affinity, the same maximum tumor content and uptake ratio were achieved but progressively earlier. At high affinity there was a substantial advantage for a small ligand compared with whole antibody in terms of uptake ratio (550 versus 100) and tumor:normal tissue integral dose ratio (330 versus 60). The uptake of a small ligand was not increased by binding to plasma protein but with increasing time the tumor content was higher than without protein binding.
Animals↗
Biomaterials entrepreneurship.
Entrepreneurial companies in biomaterials serve a valuable function in lowering the risk of developing new products and devices. In many cases liability considerations and a pragmatic conservatism make it difficult for established health-care products suppliers to develop new products directly. Biomaterials entrepreneurs encounter more difficulties in achieving commercial success than do entrepreneurs in other fields. For any reasonable profit to be made, the entrepreneur must be able to convert the biomaterial into a useful device. Safety and toxicity test data collection take a minimum of three years to collect, and it is often five or more years before a positive cash flow can be obtained. Start-up funding can be obtained from government agencies, charitable foundations, and private investment capital. A major health-care company can often be attracted once initial successes have been achieved. Biomaterials usage and device design is specific for each function or need. Specific devices that are currently needed are small (c. 4 mm) diameter artificial blood vessels, synthetic skin, and internal prosthetic devices which have better tissue compatibility, abrasion, corrosion, and wear resistance especially for flexing devices such as artificial joints, ligaments and tendons.
Biocompatible Materials↗
Professional growth: 5 ways to prevent malpractice claims.
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Humans↗
Optimal background estimation in EELS.
In quantitative electron energy loss spectrometry, it is desirable to estimate the background law below core edge energy in a way that provides the maximum signal-to-noise ratio. Assuming an inverse power background model and independently Poisson distributed measurements, it is shown how to achieve this goal by using a maximum likelihood (ML) estimation technique which provides unbiased and minimum mean square error estimates of all parameters of interest. An efficient and computationally stable implementation of this procedure is proposed. Standard logarithmic least squares estimations are then compared with the ML approach and the gain in performance due to optimal processing is quantified.
Electrons↗
Weighted least squares estimation of background in EELS imaging.
In quantitative Electron Energy Loss Spectrometry, a weighted least squares estimation should theoretically be used to estimate the background law below core edge energy, since the variances of the data vary. However, it is found that proper weighting makes the above edge signal-to-noise ratio decrease rather than increase. This result is discussed, and the influence of the bias introduced by the logarithmic transformation of the data is quantified.
Spectrum Analysis↗
Analysis of emission tomographic scan data: limitations imposed by resolution and background.
The proper analysis of positron emission tomographic scan data requires a careful knowledge of the limitations of the tomographic system used so that scan data can be collected and sampled in a manner consistent with those limitations. The present investigation was undertaken to clarify some of the limitations imposed by resolution. The usual imaging situation, e.g., 218FDG , C15O2, or 15O2 , involves imaging structures of limited size in all three dimensions which may appear either warm or cool in relation to some background level of activity. In emission tomography the importance of adequate data sampling within a given plane has been frequently emphasized. Little attention, however, has been given to proper z axis sampling for clinical scanning. The actual selection of regions of interest from scans can have a significant impact on the subsequent statistical analysis. Previous work on this subject has experimentally examined the relationship of object size to quantitative estimation in the hot spot-cold background situation for the one- and two-dimensional cases. Approximate three-dimensional recovery coefficients for the hot spot-cold background situation have been calculated. An examination of the factors discussed above, three-dimensional objects with varying contrast, z axis sampling, and selection of regions of interest, has not yet been addressed in the literature. The purpose of the present investigation is to examine these factors.
Background Radiation↗
Optimized acquisition parameters and statistical detection limit in quantitative EELS.
Optimizing the acquisition parameters for EELS recording has to be accomplished simultaneously from the physical and the statistical points of view; the statistical aspect of the question is covered here. Approximate probability density functions of the variables of interest are derived, which provide a global measure of signal-to-noise ratio taking into account every step of the EELS edge area estimation process. Qualitative and quantitative advice is given regarding the critical choice of the estimation and integration energy regions. The notion of visual contrast is presented; it permits the introduction of the concept of statistical detection limit. It is found that for typical experimental conditions, when other factors are equal, the required analysis time for the sample varies approximately as the inverse square of the concentration.
Electron Probe Microanalysis↗
Mitochondrial toxicity of 2,5-diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone.
2,5-Diaziridinyl-3,6-bis-(carboethoxyamino)-1,4-benzoquinone (AZQ) is an antitumor agent characterized by lipid solubility and the ability to penetrate the central nervous system. Two human glioma-derived cell lines, SNB-1 and SNB-2, proved by microcytotoxicity assay to be sensitive to AZQ, were examined with transmission electron microscopy for morphologic changes induced by this drug. AZQ was used in two ways: a) dissolved with dimethylacetamide (aqueous) at concentrations of 25 and 50 micrograms/ml and b) solid (surface plated) at 3.1 and 6.2 micrograms/mm2. A time study from 30 minutes to 48 hours was performed. Selective mitochondrial destruction was noted after 8 hours of exposure to AZQ. After 12 hours, condensation of chromatin along the periphery of the nucleus and dilation of endoplasmic reticulum were two other cellular reactions observed. Thus in addition to the known alkylating activity of AZQ, it has significant mitochondrial toxicity. This antimitochondrial effect is possibly an important factor in the antiglioma cell cytotoxicity of AZQ.
Antineoplastic Agents↗
The Pickering survey. A distressing picture.
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Curriculum↗
A method of artificial eye manufacture.
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Eye, Artificial↗
Human values in medical education.
Attitudes and values in medicine vary with the nature of the individual, his education and training, and the circumstances of his professional life. Comparisons are drawn between medical education in Britain 40 years ago and today. Though education has changed, British students are still mainly motivated by a desire to care for sick people. The impact of personal medicine on a country that has long accepted the need for some kind of national health service is described. It is postulated that as government and public become increasingly involved in health care, it is of paramount importance that medical education should provide a clear understanding of what a profession is and inculcate a determination to maintain true professional status. New responsibilities of the profession, to the public at large and to society, are suggested. The ability of medical education to exert a good influence on concern for human values in medicine depends in the final analysis on the ability to show excellence to medical students.
Attitude of Health Personnel↗
The cutaneous reactions to kallikrein, prostaglandin and thurfyl nicotinate in chronic urticaria and the effect of polyphloretin phosphate.
The erythema and wealing resulting from the application of thurfyl nicotinate ointment (Trafuril) and from the inoculation of kallikrein has been studied in patients with chronic urticaria and normal controls. Polyphloretin phosphate (PPP) suppressed the reaction in controls but in patients with urticaria it increased the reactions to Trafuril and had little effect on the kallikrein reaction. PPP also suppressed the PGE2-induced erythma in normal controls but not in urticaria patients. In a separate study using fibrinolysis autography, prostaglandin (PG) E2 and PGF2alpha depressed fibrinolysis in the skin of two pigs and both kallikrein and Trafuril suppressed fibrinolysis in human skin. It is suggested that the inflammatory reaction induced by thurfyl nicotinate and kallikrein is mediated in part by a prostaglandin-like action. Several anomalies in the action of Trafuril in skin diseases can be explained if such prostaglandin-like activity is mediated in part through inhibition of fibrinolysis.
Chronic Disease↗