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Biomedical subjects

R Wootton

Publications and source records attributed to R Wootton.

195 records · Page 11Linked to original sources
PubMed1976

Compounds designed to fit a site of known structure in human haemoglobin.

1 The three-dimensional coordinates of the atoms in human haemoglobin are known, and there is a specific site in the deoxygenated form of the protein at which 2,3-diphosphoglycerate (DPG) interacts. 2 Molecular models of this site have been constructed and used to design compounds which should bind to the deoxy conformation and stabilize it. These compounds should therby promote oxygen liberation, as does DPG. 3The compounds so designed were found to promote oxygen liberation. Their relative potencies, as assessed by sigmoidal dose-response curves, are in the predicted sequence.

Benzyl Compounds↗
PubMed1976

The limitations of 113Inm for plasma volume measurement.

Previous authors have claimed that 113InmCl3 is a valid tracer for plasma volume measurement. However, careful measurements in haematologically normal volunteers and in rabbits, using 125I-labelled human serum albumin as a reference tracer, show that the results obtained with 113Inm-chloride, -citrate or -transferrin consistently over-estimate the plasma volume and are probably no better than can be predicted from the height and weight of the subject.

Animals↗
PubMed1975

Physiochemical-activity relations in practice. 1. A rational and self-consistent data bank.

A data bank of substituent constants of 26 ortho and 34 meta and para benzenoid substituents is presented for use in physicochemical-activity relations (PAR) studies. The distributive parameters pri and pri-, a bulk parameter based on molar refraction, and positionally weighted electronic parameters F and R are listed for the three substituent positions. There are no gaps in the table caused by missing values and the interparameter correlation are low.

Chemical Phenomena↗
PubMed1975

Physicochemical-activity relationship in practice. 2. Rational selection of benzenoid substituents.

A rational method is presented for the selection of substituents to be introduced into a benzenoid ring system of a biologically active compound in order to a defined physicochemical parameter space. The method, which may be readily programmed for use on a computer, relies on maintaining a minimum distance between compounds in the multidimensional physicochemical parameter space. The series of compounds produced will then have a well-spread set of minimally correlated physicochemical parameter values and could thus be used for the reliable correlation of the variation in the biological activities of the members of the series with changes in these physicochemical parameters. Some examples of the use of the present method under various conditions are given, and it is compared with alternatives in the literature.

Benzene Derivatives↗
PubMedDate not supplied

Observer variation in quantification of immunocytochemistry by image analysis.

This paper reports the findings of a study designed to examine observer variation as a source of inaccuracy inherent in the use of computer-assisted image analysis to measure areas of stained tissue. The rat pituitary immunostained for prolactin and galanin was used as an example to estimate patterns of immunoreactivity exhibited by different cell types. Six observers, with differing experience, selected grey level threshold values on 40 fields of images of stained tissue making three repeats of each field. The 40 fields consisted of 20 serial pairs of colocalized fields, one immunostained for prolactin, the other for galanin. The 20 pairs consisted of four pairs from each of five animals. Analysis of observer variation in the selection of threshold values showed large differences in the within- and between-observer variation. Analysis of the components of variance in the estimation of the ratios of stained tissues showed that the major source of variation was the within-observer component. An additional experiment using two observers, where half of the images were compared to the original microscope images before setting threshold levels, showed that the opportunity to make a comparison did not reduce observer variation. It is suggested that any study which uses semi-automatic methods to segment regions of a digital image can benefit from an analysis of this kind so that the sources of variation can be determined to enable maximum discriminating power in future studies.

Animals↗
PubMedDate not supplied

Studies of a single placental cotyledon in vitro: II. The intravascular volume.

The intravascular volume of isolated perfused human placental cotyledons was measured by the mean transit time of injected radio-iodine labelled human serum albumin. The technique gives highly reproducible results with no evidence of change with time. The mean intravascular volume was about 6 ml per 100 g of tissue, some 20 ml for an average placenta at term.

Blood Vessels↗
PubMedDate not supplied

Studies of a single placental cotyledon in vitro: III. The dimensions of the villous capillaries.

The capillary beds of ten isolated perfused placental cotyledons were examined by injecting microspheres ranging from 2 microgram to more than 20 microgram diameter into the villous circulation. As many as 25 per cent of capillaries may be less than 4 microgram in diameter; there are virtually none whose diameter exceeds 11 microgram and there is no evidence of large diameter vascular shunts.

Capillaries↗
PubMedDate not supplied

Measurement of unidirectional transplacental flux: a simplified method.

A simple method for determining unidirectional transplacental flux in the in vitro perfusion (transfer factor analysis) has been derived from a general treatment of non-compartmental analysis describing transfer between two accessible pools. This method was validated by comparison of the unidirectional transfer fractions for Evans Blue in a two-pool hydraulic model with the true transfer fractions determined from the pump flow rates in the model. There was excellent agreement between calculated and true transfer fractions. Transfer fractions obtained using this method were also compared to the fractions determined by a previously described technique, deconvolution analysis, for a hydraulic model in which a third, inaccessible pool was interposed between the two accessible pools. Good agreement was found between the two methods. Similar agreement was found for the fractional transfer of [14C]L-lactate in the in vitro perfused human placenta, calculated using transfer factor and deconvolution analysis. The sample collection and data processing are much simpler using the former method but the quality of information obtained is reduced accordingly.

Female↗
PubMedDate not supplied

Lactate transfer across the perfused human placenta.

The transfer of lactate across the human placenta was investigated using an in vitro dually-perfused placental preparation. Using a novel technique, the unidirectional flux of L-lactate was found to be linearly dependent on L-lactate concentration. In addition, unidirectional transfer rates were found to be the same in both maternal-to-fetal and fetal-to-maternal directions at the same lactate concentration. Transfer of [14C]L-lactate was decreased by approximately 15 per cent in competition with unlabelled L-lactate. Stereospecificity and permeability experiments demonstrated the existence of a transfer mechanism which could distinguish between the L- and D-isomers of lactate. Our data suggest that, while a stereospecific carrier for lactate exists in the perfused placenta, the bulk of transplacental lactate transfer takes place by non-carrier-mediated diffusion.

Antipyrine↗
PubMedDate not supplied

Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans.

To assess the potential of various plasma lipoprotein classes to contribute to the lipid content of the arterial intima, influx and efflux of these plasma lipoprotein fractions into and from the intima of human carotid arteries were measured in vivo. While low density lipoprotein (LDL) is known to transfer from plasma into the arterial wall, there is less information on the atherogenic potential of lipoproteins of intermediate density (Sf 12-60) or of very low density (Sf 60-400). Aliquots of the same lipoprotein (LDL, Sf 12-60 lipoprotein particles, or Sf 60-400 lipoprotein particles) iodinated with iodine-125 and iodine-131 were injected intravenously 18-29 hours and 3-6 hours, respectively, before elective surgical removal of atheromatous arterial tissue, and the intimal clearance of lipoproteins, lipoprotein influx, and fractional loss of newly entered lipoproteins were calculated. Intimal clearance of Sf 60-400 particles was not detectable (less than 0.3 microliter x hr-1 x cm-2), whereas the average value for both LDL and Sf 12-60 lipoprotein particles was 0.9 microliter x hr-1 x cm-2. Since the fractional loss of newly entered LDL and Sf 12-60 lipoprotein particles was also similar, the results suggest similar modes of entry and exit for these two particles. However, due to lower plasma concentrations of Sf 12-60 lipoproteins as compared with LDL, the mass influx of cholesterol in the Sf 12-60 particles was on the order of one 10th of that in LDL, and that of apolipoprotein B was about one 20th.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMedDate not supplied

Pathological features of intra-uterine growth retardation in the piglet: differential effects on organ weights.

The body and organ weights of twenty-four intra-uterine growth retarded neonatal piglets were compared with those of seventeen normal littermate controls. There was a highly significant relation between organ weight and body weight for the following organs which all showed a reduction as body weight decreased: liver, kidneys, heart, lungs, spleen and pancreas. In contrast, brain, pituitary, adrenal and thyroid weights did not change significantly with body weight implying preferential protection from the pathological effects of intra-uterine growth retardation. Our results also show that the pattern of natural growth retardation in the piglet is similar to that reported in man, and to that of the experimental growth retardation produced in a number of animal species.

Animals↗