Showing papers by "University College London published in 1988"
TL;DR: Monte Carlo modelling of light pulses in tissue has shown that the mean value of the time dispersed light pulse correlates with the pathlength used in quantitative spectroscopic calculations, and this result has been verified in a phantom material.
Abstract: Quantitation of near infrared spectroscopic data in a scattering medium such as tissue requires knowledge of the optical pathlength in the medium. This can now be estimated directly from the time of flight of picosecond length light pulses. Monte Carlo modelling of light pulses in tissue has shown that the mean value of the time dispersed light pulse correlates with the pathlength used in quantitative spectroscopic calculations. This result has been verified in a phantom material. Time of flight measurements of pathlength across the rat head give a pathlength of 5.3+or-0.3 times the head diameter.
2,068 citations
TL;DR: Patterns of anatomical connections in the visual cortex form the structural basis for segregating features of the visual image into separate cortical areas and for communication between these areas at all levels to produce a coherent percept.
Abstract: Patterns of anatomical connections in the visual cortex form the structural basis for segregating features of the visual image into separate cortical areas and for communication between these areas at all levels to produce a coherent percept. Such multi-stage integration may be a common strategy throughout the cortex for producing complex behaviour.
1,039 citations
TL;DR: The cytochrome aa3 spectrum in vivo from the brains of rats after replacing the blood with a fluorocarbon substitute is obtained and an algorithm for calculating the changes in oxygenated and deoxygenated haemoglobin and oxygenated cy tochrome a a3 in tissue from changes in near IR absorption is constructed.
949 citations
TL;DR: The design and performance of an instrument that has been developed to apply the technique of near-infra-red spectroscopy to the monitoring of the brain in newborn infants are described.
Abstract: The technique of near-infra-red spectroscopy allows safe continuous monitoring of changes in blood and tissue oxygenation on an intact organ This is made possible by observing spectral changes in the tissues caused by oxygenated haemoglobin [HbO2], deoxygenated haemoglobin [Hb] and cytochrome aa3 [Cyt aa3] The paper describes the design and performance of an instrument that has been developed to apply this technique to the monitoring of the brain in newborn infants The instrument monitors optical transmission changes across a newborn infant's brain at four wavelengths A standard deviation in error of 1 per cent (0·01 optical density OD) is achieved on measurements of transmission changes at 20s intervals This performance is obtained at a mean attenuation of 10 OD, the approximate attenuation across a term infant's head Long-term monitoring is possible as instrumental drift is less than 0·004 OD per hour
941 citations
Journal Article•
TL;DR: It is concluded that cyclosporin A is a potent inhibitor of the pore and therefore Ca2+-dependent pore opening in the inner membrane of heart mitochondria is inhibited.
Abstract: The capacity of cyclosporin A to inhibit opening of a Ca2+-dependent pore in the inner membrane of heart mitochondria was investigated. Whereas in the presence of 25 nmol of Ca2+/mg of mitochondrial protein and 5 mM-Pi mitochondria were unable to maintain accumulated Ca2+, inner-membrane potential and sucrose impermeability, all three parameters were preserved when cyclosporin was included. Pore opening was assayed directly by [14C]sucrose entry and entrapment in the matrix space. [14C]Sucrose entry induced by both Ca2+ plus Pi and Ca2+ plus t-butyl hydroperoxide was almost completely inhibited by 60 pmol of cyclosporin/mg of mitochondrial protein. It is concluded that cyclosporin A is a potent inhibitor of the pore.
849 citations
TL;DR: If experimental glycation is an adequate model of tissue damage occurring in diabetes mellitus, then these studies indicate a therapeutic role for antioxidants.
Abstract: Protein exposed to glucose is cleaved, undergoes conformational change and develops fluorescent adducts (‘glycofluorophores’). These changes are presumed to result from the covalent attachment of glucose to amino groups. We have demonstrated, however, that the fragmentation and conformational changes observed are dependent upon hydroxyl radicals produced by glucose autoxidation, or some closely related process, and that antioxidants dissociate structural damage caused by the exposure of glucose to protein from the incorporation of monosaccharide into protein. We have also provided further evidence that glycofluorophore formation is dependent upon metal-catalysed oxidative processes associated with ketoaldehyde formation. If experimental glycation is an adequate model of tissue damage occurring in diabetes mellitus, then these studies indicate a therapeutic role for antioxidants.
811 citations
TL;DR: It is shown that platelet-derived growth factor (PDGF) can replace type-1-astrocyte-conditioned medium in restoring the normal timing of oligodendrocytes differentiation in vitro and that anti-PDGF antibodies inhibit this property of the appropriately conditioned medium.
Abstract: The various cell types in a multicellular animal differentiate on a predictable schedule but the mechanisms responsible for timing cell differentiation are largely unknown. We have studied a population of bipotential glial (O-2A) progenitor cells in the developing rat optic nerve that gives rise to oligodendrocytes beginning at birth and to type-2 astrocytes beginning in the second postnatal week. Whereas, in vivo, these O-2A progenitor cells proliferate and give rise to postimitotic oligodendrocytes over several weeks, in serum-free (or low-serum) culture they stop dividing prematurely and differentiate into oligodendrocytes within two or three days. The normal timing of oligodendrocyte development can be restored if embryonic optic-nerve cells are cultured in medium conditioned by type-1 astrocytes, the first glial cells to differentiate in the nerve: in this case the progenitor cells continue to proliferate, the first oligodendrocytes appear on the equivalent of the day of birth, and new oligodendrocytes continue to develop over several weeks, just as in vivo. Here we show that platelet-derived growth factor (PDGF) can replace type-1-astrocyte-conditioned medium in restoring the normal timing of oligodendrocyte differentiation in vitro and that anti-PDGF antibodies inhibit this property of the appropriately conditioned medium. We also show that PDGF is present in the developing optic nerve. These findings suggest that type-1-astrocyte-derived PDGF drives the clock that times oligodendrocyte development.
765 citations
TL;DR: It is proposed that astrocyte-derived PDGF is crucial for the control of myelination in the developing central nervous system.
751 citations
TL;DR: TRACP-positive multinucleated cells formed in response to osteotropic hormones in mouse marrow cultures satisfy most of the criteria of osteoclasts, and osteoblasts may play an important role in osteoclast formation.
Abstract: We developed a mouse bone marrow culture system to examine the process of osteoclast-like multinucleated cell formation from its progenitors. When mouse marrow cells were cultured for 8 days with 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3, 10(-10) to 10(-7) M] or human PTH (1-34) (25-100 ng/ml), tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells formed. No TRACP-positive multinucleated cells appeared in the absence of these hormones. 1 alpha,25-(OH)2D3 and PTH also increased the number of the clusters of TRACP-positive mononuclear cells. Time course studies showed that these TRACP-positive mononuclear cell clusters appeared before the formation of TRACP-positive multinucleated cells, suggesting that the TRACP-positive mononuclear cells are precursors of the multinucleated cells. Salmon calcitonin markedly inhibited the formation of TRACP-positive multinucleated cells but not TRACP-positive mononuclear cell clusters induced by 1 alpha,25-(OH)2D3 or PTH. TRACP-positive mononuclear cells and multinucleated cells were rarely stained for nonspecific esterase, but some mononuclear cells were positively stained for both nonspecific esterase and TRACP. More that 90% of the TRACP-positive mononuclear cell clusters and multinucleated cells were found near colonies of alkaline phosphatase-positive mononuclear cells (possibly osteoblasts). When marrow mononuclear cells were cultured on sperm whale dentine slices in the presence of 1 alpha,25-(OH)2D3 or PTH, numerous resorption lacunae were formed. These results suggest that 1) TRACP-positive multinucleated cells formed in response to osteotropic hormones in mouse marrow cultures satisfy most of the criteria of osteoclasts, and 2) osteoblasts may play an important role in osteoclast formation.
749 citations
TL;DR: Although the Affective theory makes better sense of the results from emotional recognition tasks, the Cognitive theory predicts the particular pattern of impaired and unimpaired social skills in autism, as well as the pragmatic deficits.
Abstract: Autism is characterized by a chronic, severe impairment in social relations. Recent studies of language in autism also show pervasive deficits in pragmatics. We assume, uncontroversially, that these two deficits are linked, since pragmatics is part of social competence. This paper reviews the literature describing these deficits, and then considers two different psychological theories of these phenomena: the Affective theory and the Cognitive theory. Although the Affective theory makes better sense of the results from emotional recognition tasks, the Cognitive theory predicts the particular pattern of impaired and unimpaired social skills in autism, as well as the pragmatic deficits. These two theories might usefully be integrated in the future.
656 citations
TL;DR: It is suggested that these oligomers assemble from preformed monomers with little change in conformation, and in oligomers with large interfaces, isolated subunits should be unstable given their excessively large accessible surface, and assembly is expected to require major structural changes.
TL;DR: An alternative display is suggested which represents intervals as points on a bivariate graph, and which has advantages when the data are estimates of odds ratios from studies with a binary response.
Abstract: To display a number of estimates of a parameter obtained from different studies it is common practice to plot a sequence of confidence intervals. This can be useful but is often unsatisfactory. An alternative display is suggested which represents intervals as points on a bivariate graph, and which has advantages. When the data are estimates of odds ratios from studies with a binary response, it is argued that for either type of plot, a log scale should be used rather than a linear scale.
TL;DR: This work proposes two steps in nuclear migration of proteins: rapid binding around the nuclear envelope, possibly to pore-associated fibrils, followed by slower, energy-dependent translocation through nuclear pores.
TL;DR: In this article, the authors present results from the Greenwich Open Space Society (GLSS) Open Space Challenge 2016, which was held at the University of Greenwich in the UK in 2014.
Abstract: Contemporary provision of open spaces within cities rests largely on professional assumptions about its significance in the lives of residents. This paper presents results from the Greenwich Open S...
TL;DR: The unique properties of various cell division cycle mutants are used to investigate further the function of these different microtubule arrays and their temporal and positional control.
Abstract: We have characterized the changes in microtubule organization that occur through the cell division cycle of the fission yeast Schizosaccharomyces pombe by indirect immunofluorescence microscopy. During interphase, groups of cytoplasmic microtubules, independent of the spindle pole body (SPB), form an array extending between the cell tips. These microtubules are involved in positioning the nucleus at the cell equator and in the establishment of cell polarity. At mitosis, the interphase array disappears and is replaced by an intranuclear spindle extending between the now duplicated SPBs. Elongation of the spindle sees the appearance of astral microtubules emanating from the cytoplasmic face of the SPBs. These persist until the end of anaphase whereupon the spindle microtubules depolymerize and two microtubule organizing centres (MTOCs) at the cell equator re-establish the interphase array. We have used the unique properties of various cell division cycle mutants to investigate further the function of these different microtubule arrays and their temporal and positional control.
TL;DR: Non invasive infrared spectroscopy is a well established technique for monitoring changes in the oxygenation status of tissues by observing the absorption of haemoglobin and cytochrome aa3 respectively and it has normally not been possible to quantitate the observed changes.
Abstract: Non invasive infrared spectroscopy is a well established technique for monitoring changes in the oxygenation status of tissues (1). The technique has in particular been successfully employed to monitor changes in cerebral blood and tissue oxygenation by observing the absorption of haemoglobin and cytochrome aa3 respectively. Because of the highly light scattering nature of the tissues studied, it has normally not been possible to quantitate the observed changes.
TL;DR: It is indicated that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.
Abstract: Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.
TL;DR: This study confirms the close association between Hashimoto's thyroiditis and B cell lymphoma of the thyroid gland and suggests that this tumor belongs to the group of non-Hodgkin's lymphomas derived from MALT.
TL;DR: A model which can satisfactorily account for all of the principal changes in the leucocyte count that have been noted during and after exercise is developed and some predictions are made that can be tested experimentally, and some experiments are suggested which should help elucidate the mode of action of catecholamines and cortisol.
Abstract: Exercise is known to induce an immediate leucocytosis, the magnitude of which is related, in most instances, to the intensity and duration of the work. On finishing exercise, however, the leucocyte count may change in any one of several different ways. The pattern of postexercise changes in the leucocyte count is determined mainly by the time which has elapsed since beginning exercise, rather than the work intensity or the total work done, if, for example, exercise has been intermittent. Consideration of, firstly, the circumstances under which the plasma concentrations of catecholamines and cortisol have been found separately to correlate with the leucocyte count at the finish of exercise, and, secondly, the effects on the leucocyte count of exogenous administration of these substances has led us to develop a model which can satisfactorily account for all of the principal changes in the leucocyte count that have been noted during and after exercise. It is proposed that catecholamines produced during exercise act to increase the ratio of circulating to non-circulating leucocytes, while cortisol acts, by a mechanism which involves a time lag, to increase the total number of leucocytes in the vascular compartment. Examination of previously published reports shows that many contain results which support this model. Using the model as a basis, some predictions are made that can be tested experimentally, and some experiments are suggested which should help elucidate the mode of action of catecholamines and cortisol.
TL;DR: These surveys, originally published in the "Economic Journal", aim to provide an overview and synthesis of current work in the major fields of economics and point the way to future research.
Abstract: This survey is designed to emphasize the relationship between empirical a nd theoretical considerations in the analysis of consumer behavior. A lthough it focuses primarily on analysis at the individual or micro l evel, it tries, where possible, to draw implications for the estimati on of aggregate relationships. The importance of micro-level analysis stems from the rapid expansion in available panel and survey data se ts. This development has generated its own theoretical and empirical issues, many of which are raised in this survey. Copyright 1988 by Royal Economic Society.
TL;DR: In this article, the authors derived expressions describing the dependence of the crystallization induction period tind on supersaturation for different possible nucleation and growth mechanisms, and their validity is assessed on the basis of experimental evidence.
TL;DR: It is shown that the type-2-astrocyte-inducing protein is similar or identical to ciliary neutrotrophic factor (CNTF)8,9, which promotes the survival of some types of peripheral neurons in vitro8, including ciliary ganglion neurons8,10, which suggests that CNTF, in addition to its effect on neurons, may be responsible for triggering type-1 astrocytes differentiation in the developing CNS.
Abstract: We have been studying a population of bipotential glial progenitor cells in the perinatal rat optic nerve and brain in an attempt to understand how cells choose between alternative fates in the developing mammalian central nervous system (CNS). This cell population gives rise initially to oligodendrocytes and then to type-2 astrocytes, both of which apparently collaborate in sheathing axons in the CNS. In vitro studies suggest that oligodendrocyte differentiation is the constitutive pathway of development for the oligodendrocyte-type-2-astrocyte (O-2A) progenitor cell, whereas type-2 astrocyte differentiation depends on a specific inducing protein. This protein is present in the developing optic nerve when type-2 astrocytes are differentiating and can induce O-2A progenitor cells in vitro to express glial fibrillary acidic protein (GFAP), a marker of astrocyte differentiation. Here we show that the type-2-astrocyte-inducing protein is similar or identical to ciliary neutrotrophic factor (CNTF), which promotes the survival of some types of peripheral neurons in vitro, including ciliary ganglion neurons. This suggests that CNTF, in addition to its effect on neurons, may be responsible for triggering type-2 astrocyte differentiation in the developing CNS.
TL;DR: This work reports that glutamate uptake is activated by intracellular potassium and inhibited by extracellular potassium, and results indicate that one K+ ion is transported out of the cell each time a glutamate anion and three Na+ ions are transported in.
Abstract: Uptake of glutamate into glial cells in the CNS maintains the extracellular glutamate concentration below neurotoxic levels and helps terminate its action as a neurotransmitter The co-transport of two sodium ions on the glutamate carrier is thought to provide the energy needed to transport glutamate into cells We have shown recently that glutamate uptake can be detected electrically because the excess of Na+ ions transported with each glutamate anion results in a net current flow into the cell We took advantage of the control of the environment, both inside and outside the cell, provided by whole-cell patch-clamping and now report that glutamate uptake is activated by intracellular potassium and inhibited by extracellular potassium Our results indicate that one K+ ion is transported out of the cell each time a glutamate anion and three Na+ ions are transported in A carrier with this stoichiometry can accumulate glutamate against a much greater concentration gradient than a carrier co-transporting one glutamate anion and two Na+ ions Pathological rises in extracellular potassium concentration will inhibit glutamate uptake by depolarizing glial cells and by preventing the loss of K+ from the glutamate carrier This will facilitate a rise in the extracellular glutamate concentration to neurotoxic levels and contribute to the neuronal death occurring in brain anoxia and ischaemia
TL;DR: A graphical method is proposed to display a number of point estimates while allowing for their differing standard errors, and can be viewed as a representation of interval estimates by points on a bivariate plot.
Abstract: A graphical method is proposed to display a number of point estimates while allowing for their differing standard errors. More generally, it can be viewed as a representation of interval estimates by points on a bivariate plot. The method exploits a familiar connection between standardized estimates and regression through the origin and has several advantages over some alternative plots used in the literature. It is particularly useful when there may be a mixture of parameters, as illustrated by the problem of “mixed ages” in fission track dating.
TL;DR: In this paper, a stochastic model for rainfall at a single site is studied in which storms arrive in a Poisson process, each storm consisting of a cluster of a random number of rain cells, each cell having random duration and depth.
Abstract: A stochastic model for rainfall at a single site is studied in which storms arrive in a Poisson process, each storm consisting of a cluster of a random number of rain cells, each cell having random duration and depth. A model studied in an earlier paper is extended to provide a better fit to empirical experience, the extension being based on the attachment of a single random variable to each storm to achieve in particular some correlation between the durations of the cells within a single storm. The properties of the new model are developed, its fitting to two sets of empirical data is described and the examination of adequacy of fit is studied in some detail via properties not used in the fitting procedure. Finally a theoretical study is made of short-term prediction from the model.
TL;DR: There is strong evidence that astrocytes in the diffusely vascularized rat retina are immigrants from the optic nerve, and these immigrants derive from Miiller cells.
Abstract: The retina in most mammals contains two types of macroglial cells--Muller cells, which span the entire thickness of the retina, and astrocytes, which are mainly confined to the nerve fibre layer. Whereas Muller cells are diffusely distributed in all vertebrate retinae, the presence and distribution of retinal astrocytes correlate with the presence and distribution of retinal blood vessels: retinae that are avascular contain no astrocytes; those that are diffusely vascularized contain diffusely distributed astrocytes; and those that are vascularized in a restricted region contain astrocytes only in the vascularized region. This striking correlation between vascularization and the presence of astrocytes led Stone and Dreher to postulate that retinal astrocytes are immigrants that enter the retina with its vasculature, although others have suggested that they derive from Muller cells. Here we provide strong evidence that astrocytes in the diffusely vascularized rat retina are immigrants from the optic nerve.
TL;DR: It is concluded that heart mitochondria do contain a pore whose permeation state is controlled over an approximate 1000-fold range by Ca2+ and other factors including phosphate, oxidative stress and ADP.
Abstract: Evidence that the Ca2+-induced permeabilization of mitochondria is attributable to a reversible Ca2+-activated pore [Al Nasser & Crompton (1986) Biochem. J. 239, 19-29] has been further investigated. Permeabilization is induced in a wholly synergistic manner by either Ca2+ plus phosphate or Ca2+ plus tert-butyl hydroperoxide. When permeabilization is complete, extramitochondrial [14C]sucrose equilibrates with the matrix space with a half-time of about 800 ms; [14C]mannitol equilibrates at least threefold faster. Permeabilization is essentially fully reversed on Ca2+ chelation with EGTA, when the half time for [14C]sucrose equilibration is increased 600-1400-fold (to 550-1150 s). A pulsed-flow [14C]solute-entrapment technique has been developed to measure the kinetics of EGTA-induced resealing. The technique incorporates a suitable choice of [14C]solute and an appropriate model for data analysis, and is competent to measure permeation state changes occurring in 100 ms. The data obtained are consistent with exponential resealing of mitochondria in which pores of any single mitochondria close with a high degree of synchrony. The rate of resealing is increased about eight-fold by ADP (half-time approximately 1 s; Km approximately 30 microM). CoA, Mg2+, AMP and also ATP, when account is taken of ADP arising by hydrolysis, are essentially ineffective. It is concluded that heart mitochondria do contain a pore whose permeation state is controlled over an approximate 1000-fold range by Ca2+ and other factors including phosphate, oxidative stress and ADP. The possible involvement of the pore in reoxygenation-induced injury in heart is discussed.
TL;DR: While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.
Abstract: The monoclonal antibody Ki67 recognizes an antigen expressed in all phases of the cell cycle except Go. It has been used in 141 biopsies from 138 patients with non-Hodgkin's lymphoma to identify proliferating cells in histological sections. A Ki67 index (the number of Ki67 positive tumour cells divided by the sum of Ki67 positive and negative tumour cells) has been derived by counting 1000 cells in each case. A correction for the presence of non-tumour cells has been incorporated by counting non-tumour cells in serial sections stained with a panel of other antibodies. A very strong correlation between a low Ki67 index (less than 20 per cent) and low grade histology and a high Ki67 index (greater than 20 per cent) and high grade histology was found (Chi2 = 98.0). Ninety-one patients could be analysed for survival and those with low grade lymphoma (n = 38) who had a relatively high Ki67 index (greater than 5 per cent) had a worse survival than those with an index of less than 5 per cent (p less than 0.05). In contrast, there was a trend for those patients with high grade disease with a very high Ki67 index (greater than 80 per cent) to have a better survival than those with a lower index (less than 80 per cent). The patients with high grade disease who achieved complete remission or good partial remission and had a Ki67 index of less than 80 per cent were more likely to relapse than those with an index of greater than 80 per cent (p less than 0.04). These findings could not be explained by the effect of other prognostic factors such as age, stage, or serum albumin. While the use of Ki67 immunostaining has potential drawbacks, it appears to be a simple and reproducible method of determining a tumour proliferative index which provides relevant clinical data.