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At least 667 records · Page 37Linked to original sources
PubMed1998

Place cell discharge is extremely variable during individual passes of the rat through the firing field.

The idea that the rat hippocampus stores a map of space is based on the existence of "place cells" that show "location-specific" firing. The discharge of place cells is confined with remarkable precision to a cell-specific part of the environment called the cell's "firing field." We demonstrate here that firing is not nearly as reliable in the time domain as in the positional domain. Discharge during passes through the firing field was compared with a model with Poisson variance of the location-specific firing determined by the time-averaged positional firing rate distribution. Place cells characteristically fire too little or too much compared with expectations from the random model. This fundamental property of place cells is referred to as "excess firing variance" and has three main implications: (i) Place cell discharge is not only driven by the summation of many small, asynchronous excitatory synaptic inputs. (ii) Place cell discharge may encode a signal in addition to the current head location. (iii) The excess firing variance helps explain why the errors in computing the rat's position from the simultaneous activity of many place cells are large.

Action Potentials↗
PubMed2003

A diffusion-based theory of organism dispersal in heterogeneous populations.

We develop a general theory of organism movement in heterogeneous populations that can explain the leptokurtic movement distributions commonly measured in nature. We describe population heterogeneity in a state-structured framework, employing advection-diffusion as the fundamental movement process of individuals occupying different movement states. Our general analysis shows that population heterogeneity in movement behavior can be defined as the existence of different movement states and among-individual variability in the time individuals spend in these states. A presentation of moment-based metrics of movement illustrates the role of these attributes in general dispersal processes. We also present a special case of the general theory: a model population composed of individuals occupying one of two movement states with linear transitions, or exchange, between the two states. This two-state "exchange model" can be viewed as a correlated random walk and provides a generalization of the telegraph equation. By exploiting the main result of our general analysis, we characterize the exchange model by deriving moment-based metrics of its movement process and identifying an analytical representation of the model's time-dependent solution. Our results provide general and specific theoretical explanations for empirical patterns in organism movement; the results also provide conceptual and analytical bases for extending diffusion-based dispersal theory in several directions, thereby facilitating mechanistic links between individual behavior and spatial population dynamics.

Animal Migration↗
PubMed1995

Molecular analysis of TCR junctional variability in individual infiltrated islets of non-obese diabetic mice: evidence for the constitution of largely autonomous T cell foci within the same pancreas.

Insulitis develops in non-obese diabetic (NOD) mice as a multicentric and asynchronous process. In an effort to understand how this T cell mediated process expands within each islet and propagates between the islets of the same pancreas, we have analyzed the junctional diversity of TCR V beta 6 and V beta 8.2 transcripts cloned from infiltrated islets. The material examined was obtained from individual islets of 8 and 12 week old NOD mice or from pooled islets of 4 week old individual mice. Compared with spleen transcripts, where every V beta 6 or V beta 8.2 clone displays a different junction, islet transcripts are considerably less diverse. Each islet harbors from one to a maximum of six independent CDR3 sequences out of 10 or more analyzed colonies. On the other hand, there is an overall diversity of sequences when comparing the islets of the same pancreas or individual mice at 4 weeks. Altogether, these results support the idea that TCR repertoires are already divergent at the very early onset of insulitis and that each islet-centered infiltrate develops rather autonomously from the oligoclonal expansion of a limited set of precursors. Recirculation between islets is limited and does not seem to be the main mode of propagation of insulitis. Finally, a close analysis of J beta usage and N additions in beta chain transcripts from infiltrating cells reveals definite biases suggestive of an ongoing selective process imposed upon intra-pancreatic T lymphocytes.

Amino Acid Sequence↗
PubMed2005

Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals.

The majority of maturing T lymphocytes that recognize self-antigens is eliminated in the thymus upon exposure to their target antigens. This physiological process of negative selection requires that tissue-specific antigens be expressed by thymic cells, a phenomenon that has been well studied in experimental animals. Here, we have examined the expression in human thymi of four retinal antigens, that are capable of inducing autoimmune ocular disease retinal S-antigen (S-Ag), recoverin, RPE65 and inter-photoreceptor retinoid-binding protein (IRBP)], as well as four melanocyte-specific antigens, two of which are used as targets for melanoma immunotherapy [gp100, melanoma antigen recognized by T cells 1, tyrosinase-related protein (TRP)-1 and TRP-2]. Using reverse transcription (RT)-PCR, we found that all thymic samples from the 18 donors expressed mRNA transcripts of most or all the eight tested tissue antigens. Yet, the expression of the transcripts varied remarkably among the individual thymic samples. In addition, S-Ag, RPE65 and IRBP were detected by immunostaining in rare cells in sections of human thymi by antibodies against these proteins. Quantitative real-time RT-PCR analysis revealed that the retinal antigen transcripts in the human thymus are present at trace levels, that are lower by approximately five orders of magnitude than those in the retina. Our observations thus support the notions that thymic expression is a common feature for all tissue-specific antigens and that the levels of expression play a role in determining the susceptibility to autoimmunity against these molecules.

Antigens, Neoplasm↗
PubMed2000

Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems.

OBJECTIVES: The objectives of this article are to introduce and explore a novel paradigm based on complex nonlinear systems, and to evaluate its application to critical care research regarding the systemic host response and multiple organ dysfunction syndrome (MODS). DATA SOURCES: Published original work, review articles, scientific abstracts and books, as well as our personal files. STUDY SELECTION: Studies were selected for their relevance to the applications of nonlinear complex systems, to critical care medicine, and to the concepts presented. DATA EXTRACTION: We extracted all applicable data. DATA SYNTHESIS: Following a brief review of MODS, an introduction to complex nonlinear systems is presented, including clear concepts, definitions, and properties. By examining the multiple, nonlinear, interrelated, and variable interactions between the metabolic, neural, endocrine, immune, and inflammatory systems; data regarding interconnected antibody networks; and the redundant, nonlinear, interdependent nature of the inflammatory response, we present the hypothesis that the systemic host response to trauma, shock, or sepsis must be evaluated as a complex nonlinear system. This model provides a new explanation for the failure of trials using various antimediator therapies in the treatment of patients with sepsis and MODS. Understanding the host response as a complex nonlinear system offers innovative means of studying critical care patients, specifically by suggesting a greater focus on systemic properties. We hypothesize that analysis of variability and connectivity of individual variables offer a novel means of evaluating and differentiating the systemic properties of a complex nonlinear system. Current applications of evaluating variability and connectivity are discussed, and insights regarding future research are offered. CONCLUSION: The paradigm offered by the study of complex nonlinear systems suggests new insights to pursue research to evaluate, monitor, and treat patients with MODS.

Critical Care↗
PubMed1992

Demographical, odontological, and psychological variables in individuals referred for osseointegrated dental implants.

Edentulism and/or the wearing of a removable denture always requires adaptation, not only on a functional, but also on an emotional, level. Four hundred and seventy-three patients referred for treatment with osseointegrated implants due to problems with removable prostheses entered the study and 315 (66.6%) completed it. The average age was close to 60 yr, and the majority of patients were women. The average time of edentulousness was 14.3 yr. Twelve percent experienced profound negative effects from wearing dentures, this to an extent that it led to overt psychological and social effects. Subjective ratings revealed that functional and/or intra-personal effects were of higher significance than social consequences. The group was found to be more depressed than average as well as having an external health locus of control orientation.

Adaptation, Psychological↗
PubMedDate not supplied

Variability in individual serum cholesterol response to change in diet.

Few systematic data are available on the range of individual blood lipid responsiveness to specific diet changes. Multiple, carefully standardized total serum cholesterol (TC) measurements were made in 58 men under a variety of controlled dietary conditions. Responsiveness was defined for each individual as the change in mean TC per unit change in Diet Score based on the Keys-Minnesota equation. Only 3% were potentially "nonresponders," and even these probably evidenced some response. Of the group, 64% responded within 30% of prediction. We classed 9% as hyporesponders, while in another 9% responsiveness exceeded 1.5 times expectation. We conclude that in metabolically normal individuals the variation in short-term response to dietary change is normally distributed but that nonresponse to diet change is rare. Because metabolic, intrinsic hyporesponsiveness of TC to change in diet composition is uncommon, assessment of the real effectiveness of a dietary regimen in an individual is best based on observed dietary changes. TC changes among individuals under treatment should be based on multiple determinations and interpreted with caution.

Cholesterol↗
PubMed2005

Does genotype predict phenotype in Rett syndrome?

Mutations in the X-linked gene encoding the methyl-CpG binding protein MeCP2 are the primary cause of classic and atypical Rett syndrome and have recently been shown to contribute to other neurodevelopmental disorders of varying severity. To determine whether there are molecular correlates to the phenotypic heterogeneity, numerous groups have performed genotype-phenotype correlation studies. These studies have yielded conflicting results, in part because they used different criteria for determining severity and classifying mutations. Evolution of the phenotype with age and variable expressivity arising from individual variability in X-chromosome inactivation patterns are among other reasons the findings varied. Nonetheless, evidence of differences in the phenotypic consequences of specific types of mutations is emerging. This review analyzes the available literature and makes recommendations for future studies.

Brain Diseases↗
PubMedDate not supplied

[Multivariate methods in the analysis of the relationships between mortality and socioeconomic, environmental, and individual behavioral variables].

This study is concerned with the relationships between geographic factors and mortality from external causes, such as environmental pollution, nutrition, and socioeconomic factors. It is based on Italian data on the mortality of adult males aged 25 years and over. The results show that "degenerative diseases, from middle age onwards, are typical sicknesses of the more highly industrialised and richer areas, [particularly] where economic development has not been accompanied by action to preserve the environment from pollution. Diseases which medical and therapeutic progress have rendered almost harmless continue to strike the populations of the poorer areas, where adequate hygienic and sanitary structures are lacking." (summary in ENG, ITA)

Adult↗
PubMed1991

Ethanol absorption across human skin measured by in vivo microdialysis technique.

Microdialysis, a new bioanalytical sampling technique enables measurement of substances in the extracellular space. This initial study investigates the technique's usefulness in the field of percutaneous absorption of solvents, using ethanol as test substance. Microdialysis probes are equipped at the tip with a semi-permeable polycarbonate membrane which permits passive diffusion of substances. Ethanol does not damage the membrane. In vitro recovery for ethanol is good. Probes were inserted via a guide into the skin of the ventral forearm in 7 volunteers. 99.5% ethanol was applied to the skin in excess in a glass reservoir. The probe was perfused at a flow of 1 microliter/min. 50 microliters samples were analysed by gas chromatography. Absorption of ethanol was demonstrated in all subjects. Values from the 9 probes inserted ranged from 10 micrograms/ml to 800 micrograms/ml. The variation may be explained by inter-test or inter-individual variability in ethanol absorption. Individual metabolic capacity may be of importance. The method opens new possibilities in the investigation of skin barrier function in man.

Chromatography, Gas↗
PubMed1990

[Individual anatomical variability of arteries of the fetal surface of human placenta].

Two hundred and ten placentas of 36-40-week-old pregnancies, terminating in birth of a functionally full-bodied child have been investigated. The placental arteries form is compared with the form of the placenta, with the place of the umbilical cord fixation, with the placental areas, with the number of the umbilical arteries, etc. A close connection is stated between the form of the placenta and its arterial bed. Round, oval, triangle placentas at a certain position of the umbilical cord root are characterized with loose forms of the arteries, while at a lateral, marginal and membranous types of the umbilical cord fixation magistral forms predominate. Curved, crescent, S-form, wavy loop-like forms of the main arterial magistral on the foetal surface of the placenta are also considered as magistral ones. The loose forms are noted in placentas with additional lobuli and in multilobular placentas. There is a definite dependence between forms of the arteries, area of the placenta and amount of cotyledons. At one marginal form one arterial magistral has been found, it successively branches along the whole placenta, at another magistral form the umbilical arteries divide into 12 sectorial branches.

Anthropometry↗
PubMed1985

A simple approach to estimate the variability of individual plasma drug concentrations in patients at a standardized multiple dosing regimen.

Equations were derived to simulate the course of plasma drug concentration versus time curves for a multiple dosing regimen of drugs with a long biological half-life in those cases when Vrel and t1/2 or k in a particular subject do not correspond to the average values underlying the calculation of a standard dose. Extreme course can be expected only when Vrel and t1/2 show deviation from the average values in the opposite direction. Thus, smaller Vrel and longer t1/2 result in an increase, greater Vrel and shorter t1/2 in a decrease in plasma drug concentration after giving the standard dose. An analysis of the course of plasma drug concentration curves at the loading phase permits the estimation of the actual t1/2 in the particular subject. As an application example, the loading phase of digitoxin is presented. The procedure allows an individual dosage adjustment on the condition that plasma drug concentration in the particular subject can be monitored regularly.

Digitoxin↗