[Biochemical phenomena of collagenosis].
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Biochemical Phenomena↗
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The effect of low dose oestrogens on short-term growth and concomitant biochemical phenomena in girls with tall stature.
Using a simple non-invasive ulnar length measuring technique a 70 to 80% decrease in ulnar growth velocity was found during one interval of 9 weeks of low dose ethinyloestradiol administration (0.050 mg daily) in girls with tall stature. This decrease in ulnar growth velocity was found to be statistically significant within 6 and even 3 weeks after starting oestrogen loading whereas the change in body growth velocity was only significant after 9 weeks. After interpreting oestrogen administration, ulnar growth velocities increased again but to values tending to be lower than before ethinyloestradiol loading. Serum alkaline phosphatase activities and plasma inorganic phosphorus and calcium levels also decreased significantly during oestrogen therapy within 9 weeks. The results found illustrate that the measuring technique used enables evaluation of the short-term effect of hormonal treatment on growth and thereby related biochemical phenomena.
Adolescent↗
Molecular electrostatic potentials: an effective tool for the elucidation of biochemical phenomena.
The electrostatic potential V(r) that is created in the space around a molecule by its nuclei and electrons (treated as static distributions of charge) is a very useful property for analyzing and predicting molecular reactive behavior. It is rigorously defined and can be determined experimentally as well as computationally. The potential has been particularly useful as an indicator of the sites or regions of a molecule to which an approaching electrophile is initially attracted, and it has also been applied successfully to the study of interactions that involve a certain optimum relative orientation of the reactants, such as between a drug and its cellular receptor. A variety of methods for calculating V(r) is available, at different levels of rigor. For large biologically active molecules, multipole expansions and superposition of potentials computed for subunits have been found to be effective. A large number of chemical and biochemical systems and processes have now been studied in terms of electrostatic potentials. Three examples of such applications are surveyed in this paper. These deal with: (a) reactive properties of nucleic acids, including their component bases; (b) biological recognition processes, including drug-receptors and enzyme-substrate interactions; and (c) chemical carcinogenesis, referring specifically to the polycyclic aromatic hydrocarbons and halogenated olefins and their epoxides. For each of these areas, examples of the use of electrostatic potentials in elucidating structure-activity patterns are given.
Adrenergic beta-Agonists↗
Hydrophobic hydrophilic phenomena in biochemical processes.
The evolution of concepts developed in the study of the hydrophobic affect is surveyed, within the more general context of solvent-induced effects. A systematic analysis of the solvent-induced contribution to the driving force for the process of protein folding has led to two important modifications in our understanding of these effects. First, the conventional concepts of hydrophobic solvation and hydrophobic interactions had to be replaced by their respective conditional effects. Second, each of the hydrophobic effects has also a corresponding hydrophilic counterpart. Some of the latter effects could contribute significantly to the total driving force for the process of protein folding, and perhaps even dominate the driving force for biochemical processes.
Biochemical Phenomena↗
Finding complex oscillatory phenomena in biochemical systems. An empirical approach.
Starting with a model for a product-activated enzymatic reaction proposed for glycolytic oscillations, we show how more complex oscillatory phenomena may develop when the basic model is modified by addition of product recycling into substrate or by coupling in parallel or in series two autocatalytic enzyme reactions. Among the new modes of behavior are the coexistence between two stable types of oscillations (birhythmicity), bursting, and aperiodic oscillations (chaos). On the basis of these results, we outline an empirical method for finding complex oscillatory phenomena in autonomous biochemical systems, not subjected to forcing by a periodic input. This procedure relies on finding in parameter space two domains of instability of the steady state and bringing them close to each other until they merge. Complex phenomena occur in or near the region where the two domains overlap. The method applies to the search for birhythmicity, bursting and chaos in a model for the cAMP signalling system of Dictyostelium discoideum amoebae.
Cyclic AMP↗
[Mathematical modelling in medicine and biology. Theoretical basis and fundamentals].
Mathematical modelling is currently a common tool in the study of physiological and biochemical systems. Its basis and fundaments are not, however, well known by the non-specialist. Its aims are to describe, explain and predict physiological and biochemical phenomena. Mathematical models provide a concise and objective description of complex dynamic processes by defining, through mathematical equations, the relationships between quantitative measurements; they indicate, also, ways to improve experimental designs, and allow the testing of hypotheses about physiological or biochemical phenomena. Mathematical models can be developed from simple non-compartmental representations to large scale multi-compartmental models. The basic steps in the formulation of a model include conceptualization, realization and solution of the model. Each step has to be verified and validated. In the case of compartmental models, mass-balance equations are used to represent each compartment. A brief review of the theory of system's analysis and the general aims of mathematical modelling is presented here. The modelling process is usually started with a definition of the problem and a parameter identification followed by the setting up of a clear conceptual model of the system. The model consists of the description of the principal flows of material (in and out) and of the main components which store, convert or transmit these flows. A selection of the class of mathematical representation follows, i.e. linear or non-linear, in order to formulate the equations relating the input and output flows of material for each individual component of the system.(ABSTRACT TRUNCATED AT 250 WORDS)
Models, Biological↗
A theoretical graph method for search and analysis of critical phenomena in biochemical systems. II. Kinetic models of biochemical oscillators including two and three substances.
Four kinetic models of hypothetical complex reactions containing minimal two-substance or three-substance oscillators were constructed on the basis of the graphical rules suggested in the preceding work. The kinetic models are thought to be a part of one of four general biochemical systems: 1) system of mutual protein phosphorylation/dephosphorylation; 2) autophosphorylation of multisubunit protein; 3) association/dissociation of proteins or protein-containing structures during protein-protein or protein-ligand interaction; and 4) two-substrate enzymatic reaction with substrate inhibition by one substrate. Graphical rules of oscillator association with surrounding medium were considered. The graphical criteria of the oscillation generator elimination and criteria of oscillation damping were obtained. Both damped and undamped oscillations of reaction components were obtained by numerical integration of the mathematical models of these reactions. The areas of changes of model parameters and variables, within which the oscillations exist, were found.
Biological Clocks↗
A theoretical graph method for search and analysis of critical phenomena in biochemical systems. I. Graphical rules for detecting oscillators.
Sufficient conditions for existence of concentration oscillations of components of complex reactions are considered on the basis of graph theory. Graphical rules were developed for detecting oscillators in kinetic schemes of complex biochemical systems. The main types of topology and principles of construction of kinetic schemes of oscillators containing two, three, and four substances are considered. The resulting oscillators might be a part of the biochemical systems of the n-th order. Under certain conditions they were found to be capable of generating oscillations of the system components.
Biological Clocks↗
Navajo Indian medicine: implications for healing.
Traditional medicine men coexist with physicians and hospitals on the 25,000 square mile Navajo Indian Reservation. Most seriously ill Navajos utilize both systems of health care. This natural experiment of coexistence emphasizes several general characteristics of all healing. Traditional ceremonies are successful because they are integrated into Navajo belief systems and meet needs of sick people not dealt with by the available Western medicine. Physicians and other healers simply remove obstacles to the body's restoration of homeostasis or, as the Navajo say, to harmony. Reductionism limits the spectrum of obstacles considered relevant (eg, causes of illness), but an alternate model might include emotional, social, or spiritual phenomena equally as significant to healing as are biochemical phenomena. In that context, nonmedical healers, as well as physicians, can potentially influence factors relevant to getting well.
Adult↗
A molecular model for axon guidance based on cross talk between rho GTPases.
To systematically understand the molecular events that underlie biological phenomena, we must develop methods to integrate an enormous amount of genomic and proteomic data. The integration of molecular data should go beyond the construction of biochemical cascades among molecules to include tying the biochemical phenomena to physical events. For the behavior and guidance of growth cones, it remains largely unclear how biochemical events in the cytoplasm are linked to the morphological changes of the growth cone. We take a computational approach to simulate the biochemical signaling cascade involving members of the Rho family of GTPases and examine their potential roles in growth-cone motility and axon guidance. Based on the interactions between Cdc42, Rac, and RhoA, we show that the activation of a Cdc42-specific GEF resulted in switching responses between oscillatory and convergent activities for all three GTPases. We propose that the switching responses of these GTPases are the molecular basis for the decision mechanism that determines the direction of the growth-cone expansion, providing a spatiotemporal integration mechanism that allows the growth cone to detect small gradients of external guidance cues. These results suggest a potential role for the cross talk between Rho GTPases in governing growth-cone movement and axon guidance and underscore the link between chemodynamic reactions and cellular behaviors.
Animals↗
Effect of acute aldosterone administration on gene expression profile in the heart.
Aldosterone is known to have a number of direct adverse effects on the heart, including fibrosis and myocardial inflammation. However, genetic mechanisms of aldosterone action on the heart remain unclear. This paper describes an investigation of temporal changes in gene expression profile of the whole heart induced by acute administration of a physiologic dose of aldosterone in the mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points after aldosterone administration using oligonucleotide microarrays and compared with those of the control animals who underwent a sham injection. A novel software tool (CAGED) designed for analysis of temporal microarray experiments using a Bayesian approach was used to identify genes differentially expressed between the aldosterone-injected and control group. CAGED analysis identified 12 genes as having significant differences in their temporal profiles between aldosterone-injected and control groups. All of these genes exhibited a decrease in expression level 1-3 h after aldosterone injection followed by a brief rebound and a return to baseline. These findings were validated by quantitative RT-PCR. The differentially expressed genes included phosphatases, regulators of steroid biosynthesis, inactivators of reactive oxygen species, and structural proteins. Several of these genes are known to functionally mediate biochemical phenomena previously observed to be triggered by aldosterone administration, such as phosphorylation of ERK1/2. These results provide the first description of cardiac genetic response to aldosterone and identify several potential mediators of known biochemical sequelae of aldosterone administration in the heart.
Aldosterone↗
[Neuropsychological sequelae of acute poisoning by pesticides containing cholinesterase inhibitors].
In recent years a number of studies have drawn attention to the possible neuropsychological sequelae stemming from acute poisoning by certain substances, namely cholinesterase inhibitors. These chemicals, carbamates and organophosphorates (OP), have been used in industry, for washing cattle, as insecticides and even as chemical agents in terrorist attacks and in wars. Nowadays, they are widely used as a pesticide and this is particularly so in regions such as the west of Almeria. The intensive farming in greenhouses carried out in this area, together with the conditions in which these products are used and handled, leads to a relatively high number of cases of poisoning. Yet this is not an isolated fact; the first clinical study to describe cases of poisoning by these substances in workers was published back in 1955. Some of the neurotoxic sequelae deriving from such intoxications are well defined: acute cholinergic syndrome, intermediate syndrome and delayed polyneuropathy provoked by OP (OPIDN). Several studies have been carried out over the past few decades to measure the long term neuropsychological disorders produced by acute poisoning by these substances, and findings suggest that both cholinesterase inhibition and other biochemical phenomena can have permanent neurotoxic consequences. This communication aims to bring some order to the data offered by the different studies by analysing and verifying the evaluation protocols followed, the results of the neurophysiological and neurocognitive biochemical measurements, the type of poisoning and the time elapsed since they occurred, so that they can be summarised and taken as guidelines for possible work to be carried out in the future.
Animals↗
Reassessment of interactions between hematopoietic receptors using common beta-chain and interleukin-3-specific receptor beta-chain-null cells: no evidence of functional interactions with receptors for erythropoietin, granulocyte colony-stimulating factor, or stem cell factor.
Mice lacking both the gene encoding the shared receptor for granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 common beta-chain (B(c)) and the gene for the IL-3 specific receptor (BIL3) were generated. This was achieved by targeting the B(c) locus in embryonic stem cells that were heterozygous for a null mutation of BIL3. Cells from mice generated with the doubly targeted embryonic stem cells were unresponsive to all 3 cytokines. Considerable previous data suggested a role for common beta-chain (beta(c)) in modulating signaling of cytokines including erythropoietin (EPO), G-CSF, and stem cell factor (SCF). However, bone marrow cells from mice lacking beta(c) and beta(IL3) showed normal responsiveness to these cytokines. Thus, there was no evidence for a biologically significant interaction between signaling via beta(c) or beta(IL3) and signaling by EPO, G-CSF, or SCF. Previously documented biochemical phenomena, including receptor transmodulation, receptor transphosphorylation, and even direct physical interaction, involving the beta(c)/beta IL-3 receptor systems do not reflect genuine interactions of physiological significance in primary hematopoietic cells. This study provided results that challenge conclusions previously established using a variety of biochemical assays. (Blood. 2000;96:1588-1590)
Animals↗
Screening for Down's syndrome.
Down's syndrome (DS) is the commonest cause of severe mental retardation in children. It is the result of trisomy of chromosome 21 which is usually a random event though it is commoner in older mothers. DS can be diagnosed by chorionic villus sampling (CVS) and amniocentesis followed by karyotyping. Because of the risks associated with these invasive procedures, they can only be offered to a high-risk group. At one time the sole basis for identifying this increased risk was maternal age, but within the past ten years a series of biochemical and ultrasound abnormalities have been shown in DS pregnancies. The biochemical abnormalities include changes in the levels of most fetal and placental products in the maternal circulation. The best-known of these changes are the reduced levels of alphafetoprotein (AFP) and oestriol (E3) and increased levels of human chorionic gonadotrophin (hCG). The mechanism underlying these biochemical phenomena is unknown. Screening programmes involving the measurement of hCG and AFP, with or without additional parameters such as E3, at 15-18 weeks of pregnancy can typically identify 60% or more of cases of DS with a screen-positive rate of 5%. The combined risk derived from the various biochemical parameters, together with maternal age, is calculated by one of a number of computer programmes which have been developed for this purpose. There has been considerable discussion as to the exact biochemical tests which should be used for DS screening. This had led to controversy as to whether measurement of E3 has a place, and whether or not measurement of the free beta-subunit of hCG should replace measurement of the intact molecule. A notable recent development is the suggestion that measurement of the urinary beta-core of the hCG could be a highly discriminatory marker. A number of factors can affect the results of biochemical screening for DS. These include maternal weight, gestational age, ethnic origin, smoking, and diabetes. In addition, abnormal levels of the biochemical products may be found in other chromosome abnormalities.
Biomarkers↗
A kinetic thermodynamic phenomenological approach to genetic expression of heat-shock proteins.
The approach of viewing complex biochemical phenomena as autocatalytic relaxation processes has been introduced previously (Liquori & Tripiciano, 1980; Liquori & Florio, 1985). In the present work this formalism is extended from its original framework regarding cell growth, to the problem of genetic expression. The case of the heat-shock response in organisms ranging from man to bacteria is discussed. Finally, we give some biochemical examples in which the new approach underlines evident temporal co-operativity.
Gene Expression Regulation↗
Neurotropism, frozen muscle grafts and other conduits.
Axonal regeneration following nerve transection requires a number of cellular and biochemical phenomena in the axons as well as the nerve cell bodies. The nerve cells must survive the trauma. Since axonal severance means amputation of a large axoplasmic volume from the remaining parts of the nerve cell, the cell body must prepare for increased synthesis of axoplasm to replace the missing parts. A sprouting process must be initiated at the level of transection. Regenerating axonal processes are to regenerate towards peripheral targets, a process regulated by an interaction between genetic mechanisms in the nerve cell body and biochemical information at the molecular level along the pathway.
Animals↗
A novel two-site enzyme immunoassay reveals the regional distributions of and developmental changes in GluR1 and NMDAR1 protein contents in the rat brain.
Glutamate receptors, including the alpha-amino-3-hydroxy-4-methylisoxazole-4-propionic acid (AMPA) and NMDA receptors, play an important role in neural development and synaptic plasticity in the brain. To date, it has been difficult to correlate accurately individual biochemical phenomena with quantitative and qualitative changes in receptors occurring in specific neurons or synapses. In the present study, we established a two-site enzyme immunoassay for two key subunits of the AMPA and NMDA receptors. Its sensitivities were extremely high, 30 pg for GluR1 and 15 pg for the NMDAR1 receptor containing the C2 exon [NMDAR1(C2)], which enabled us to measure their contents in a few milligrams of hippocampal tissue. Regional and developmental variations in receptor protein levels were much more marked than those reported for mRNA: The absolute GluR1 protein content was highest in the rat hippocampus, whereas the NMDAR1(C2) content was high in all the forebrain regions examined. GluR1 protein levels increased most markedly during the second and third weeks of postnatal life, whereas NMDAR1(C2) content increased during the first postnatal week. In the adult rat brain, the ratio of GluR1 protein to NMDAR1 protein was markedly lower in neocortical regions (approximately 2%) and the highest in cerebellum (22%). Therefore, this two-site enzyme immunoassay is a specific and unique method that enables us to measure absolute tissue contents of the glutamate receptors and will lead to further important discoveries on the biochemical alterations of these receptors.
Animals↗
Effects of taxol on human neutrophils.
Taxol, a plant alkaloid, promotes and stabilizes microtubule assembly in cells and cellfree systems. In the present study, the effects of taxol on various functional, morphologic, and biochemical phenomena in human peripheral blood PMN (Hypaque-Ficoll) were examined. Taxol (10(-7) M) inhibited PMN chemotaxis stimulated by N-formyl-methionyl-leucyl-phenylalanine (f-met-leu-phe) or endotoxin-activated serum by more than 60%. The inhibition was not readily reversed by washing, and taxol itself was not a chemoattractant, nor is it a secretagogue. Spontaneous nondirected migration, cell spreading on a glass surface, and orientation of cell organelles in response to a chemoattractant gradient were also inhibited by taxol. Taxol (10(-5) M) decreased killing of Staphylococcus aureus, but did not alter phagocytosis of heat-killed Candida or hexose monophosphate shunt activity in resting or stimulated PMN. Ultrastructural studies showed that PMN incubated in f-met-leu-phe, taxol, or both had increased (p less than 0.001) numbers of centrosome-associated microtubules, and the microtubules of cells incubated in taxol with or without f-met-leu-phe were organized into bundles. Taxol (10(-5) M) markedly inhibited post-translational tyrosinolation of alpha-chains of tubulin in both resting and f-met-leu-phe-stimulated PMN. The data indicate that taxol inhibits PMN locomotion and bacterial killing, supporting a role for microtubules in these processes. The ultrastructural and biochemical data also support the view that taxol mediates its effects on PMN by its effect on microtubules.
Alkaloids↗