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Biomedical subjects

J Wyman

Publications and source records attributed to J Wyman.

At least 19 recordsLinked to original sources
PubMed2001

Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes.

Magnetic resonance arthrography. a procedure where contrast agents containing gadolinium are administered intra-articularly, has become a useful tool in musculoskeletal diagnosis. Although considered safe for systemic use, toxicities in some tissues have been identified for both free gadolinium ion and the gadolinium chelates used as contrast. In this study, the effects of short-term exposure of articular chondrocytes to gadolinium contrast were examined by assaying for proteoglycan synthesis, cell proliferation, and apoptosis. Bovine chondrocytes were grown in monolayer culture and exposed to gadodiamide for 16 h. Proteoglycan synthesis was measured through incorporation of radiolabeled sulfate. Uptake of radiolabeled thymidine assessed cell proliferation. Apoptosis was detected using the TUNEL assay, where DNA strand breaks characteristic of apoptosis are labeled with fluorescent nucleotide. Proteoglycan synthesis was stimulated by lower dose exposure to gadodiamide. At higher doses, proteoglycan synthesis returned to baseline. Cell proliferation decreased following exposure to gadodiamide in a dose-dependent manner. Chondrocyte apoptosis was induced in a dose-dependent manner. Further work is needed to determine if these in vitro effects are present in the intact joint.

Animals↗
PubMed1996

Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers.

The cyanobacterial hepatotoxin, microcystin-LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural and biochemical changes that develop concurrently with microcystin-induced cytoskeletal disorganization, isolated rat livers were perfused with MCLR at 0.1 to 5.0 micrograms/ml for 5 to 40 min. Lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase changed over time, but trends for toxin-treated and control livers did not differ. The earliest toxin-induced ultrastructural changes, observed in livers perfused at 0.1 microgram/ml for 15-20 min or at 0.3 microgram/ml for 5-10 min, were loss of hepatocyte microvilli in the space of Disse, widening of sinusoidal fenestrae, disruption of sinusoidal endothelium, dilation of bile canaliculi with loss of microvilli, and widening of hepatocyte intercellular spaces. Lesions progressed with increasing toxin concentrations and exposure times. In livers perfused with MCLR at 0.5 microgram/ml for 10-20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of hepatocytes resulting in disrupted hepatic cords. At toxin concentrations of 2.0 or 5.0 micrograms/ml for 10-20 min, there was mild dilation of mitochondrial cristae, cytoplasmic vacuolization or invagination of plasma membranes, redistribution of organelles, and sometimes nuclear degenerative change. Some hepatocytes exhibited clusters of plasma membrane blebs radiating from round cytoplasmic structures, which may be composed primarily of condensed microfilaments.

Animals↗
PubMed1995

Effect of propylene glycol 1,2-dinitrate on cerebral blood flow in rats: a potential biomarker for vascular headache?

Two measurable indices of toxicity that can be correlated with exposure to propylene glycol dinitrate (PGDN) were evaluated along with its metabolism. Propylene glycol dinitrate was administered by rapid i.v. injection to male Fischer-344 rats. These rats demonstrated a dose-response of blood pressure (BP) to doses of PGDN ranging from 0.1 to 30 mg/kg; the maximum fall in systolic BP occurred within 1 min of dosing. The i.v. administration of PGDN to separate groups of animals resulted in an increase in cerebral blood flow that was correlated with the dose, but a clear dose-response was not obtained.

Animals↗
PubMed1993

Use of mouse hepatocytes for the flow cytometric determination of DNA levels of nuclei extracted from fresh tissue of hybrid larch (Larix x eurolepis Henry).

A rapid and reliable method is presented to release intact nuclei from small amounts (100 mg) of fresh plant tissue. Further, an accurate and readily accessible new standard is proposed. Both techniques have potential application for many plant systems. The system chosen as a standard (inbred mouse strain Balb/C or B6/AF1 hepatocyte nuclei) contains both diploid and polyploid cells. This system was applied in the flow cytometric determination of absolute nuclear DNA values of female gametophytes and in vitro propagated shoots of hybrid larch (Larix x eurolepis Henry). The amount of DNA in 2C nuclei of in vitro grown larch is 32.48 +/- 4.04 or 31.97 +/- 6.14 pg/nucleus, respectively, when calculated using the mouse hepatocyte 4C or 8C nuclear peak as a reference standard. The amount of DNA in female gametophyte nuclei is 17.47 +/- 1.33 pg DNA/nucleus when these haploid larch nuclei were analyzed with trout red blood cell nuclei as the standard. When hepatocyte 4C nuclei were used as a standard, the absolute value of DNA per haploid larch nucleus was estimated as 16.8 +/- 0.53 pg. Plant tissue with as little as 4-6 pg DNA/nucleus up to as much as 35 pg DNA/nucleus can be tested using mouse hepatocytes as a standard while retaining an optimal sample/standard ratio.

Animals↗
PubMed1993

Genetically improved potatoes: protection from damage by Colorado potato beetles.

Russet Burbank potato plants have been genetically improved to resist insect attack and damage by Colorado potato beetles (Leptinotarsa decemlineata (Say)) by the insertion of a cryIIIA gene encoding the insect control protein of Bacillus thuringiensis var. tenebrionis. A modified gene that dramatically improved plant expression of this protein was utilized. Its expression in Russet Burbank potato plants resulted in protection from damage by all insect stages in the laboratory and in dramatic levels of protection at multiple field locations. Analysis of these genetically modified potatoes indicated that they conform to the standards for Russet Burbank potatoes in terms of agronomic and quality characteristics including taste.

Amino Acid Sequence↗
PubMed1993

Evaluation of shipboard formation of a neurotoxicant (trimethylolpropane phosphate) from thermal decomposition of synthetic aircraft engine lubricant.

MIL-L-23699 lubricants that are composed principally of trimethylolpropane triheptanoate (TMP) and tricresyl phosphate (TCP) have been shown to form a neurotoxicant, trimethylolpropane phosphate (TMPP), during pyrolysis and/or combustion. Mechanistically, TMPP is thought to irreversibly inhibit the GABA-mediated inhibitory response and thereby produce epileptiform clonic/tonic seizures with convulsions followed by death. Thermal decomposition of MIL-L-23699 lubricant produces TMPP under laboratory conditions, but this product has not been detected in the workplace following actual fires. This study has examined whether TMPP is produced during an actual shipboard fire by placing the synthetic lubricant in a fire environment aboard the ex-U.S.S. Shadwell, Mobile, Alabama. Both biological and chemical analyses were performed on the thermally decomposed lubricant to ensure detection of the neurotoxic material. Under the conditions of this study, the formation of TMPP during a shipboard fire was confirmed. The implications of this finding for safe management of post-fire cleanup are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed1992

Symmetry conditions for binding processes.

Symmetry conditions are derived for global and local binding processes in biological macromolecules. It is shown that the conditions applying in the case of the macromolecule as a whole are decoupled from those referring to individual sites. In the case of two sites, the global binding curve is always symmetric, and the individual-site binding curves are always asymmetric, unless the two sites are identical or independent. In the case of three sites or more, individual-site binding curves can show symmetric or asymmetric behavior. The conditions derived for symmetry in the local description of binding processes also apply to the case of linkage among different ligands and to steady-state kinetics. Application to the analysis of oxygen binding to human hemoglobin under physiological conditions provides a model-independent interpretation of the asymmetric nature of the binding curve. Asymmetry of the global binding curve can coexist with symmetric or asymmetric binding to the individual alpha and beta chains. If the binding curves of the two chains are symmetric, then subunit heterogeneity and asymmetric interactions must exist in the hemoglobin tetramer. On the other hand, if the binding curves of the two chains are asymmetric, then subunit heterogeneity and asymmetric interactions are not necessary for global asymmetric binding.

Allosteric Regulation↗
PubMed1991

Global and local metric geometry of ligand binding thermodynamics.

An abstract metric representation of ligand binding thermodynamics reveals the basic connections between the classical thermodynamic theory of binding and linkage [Wyman, J. (1964) Adv. Protein Chem. 19, 223-286] and its site-specific formulation [Di Cera, E. (1990) Biophys. Chem. 37, 147-164]. These two approaches are limit cases of a general metric formulation of binding and linkage that also includes a number of intermediate "mixed" representations.

Journal Article↗
PubMed1989

Limit-cycle oscillations and chaos in reaction networks subject to conservation of mass.

A cyclic network of autocatalytic reactions involving an unbuffered cofactor and a number of components subject to conservation of mass displays a surprising richness of dynamical behaviors. Limit-cycle oscillations are possible over a wide range of parameter values. Additionally, a cascade of period-doubling bifurcations leading to chaos can coexist with a multiplicity of stable steady states. These results draw attention to the role of unbuffering as a feedback in biochemical systems.

Chemical Phenomena↗
PubMed1988

Quantitative analysis of linkage in macromolecules when one ligand is present in limited total quantity.

We present a general framework for analysis of two closely related problems in biochemical studies: (1) The first is analysis of binding data obtained under conditions in which a second, linked ligand is present in limited total quantity. In such conditions the free activity of the second ligand varies throughout the primary ligand binding curve, and the resultant behavior can be quite complex. Analysis of such curves enables one to quantitatively extract detailed information regarding the linkage of the two ligands at intermediate stages of ligation. The treatment is applied in an accompanying paper to oxygen binding in human hemoglobin in the presence of organic phosphates [Robert, C.H., Fall, L., & Gill, S. J. (1988) Biochemistry (following paper in this issue)]. (2) The second treatment we outline regards the analogous problem of analyzing differential scanning calorimetry (DSC) data obtained for a macromolecule binding a ligand present in limited quantity. A simple model is presented that accounts for dual transitions like those already seen in DSC data for human serum albumin in the presence of nonsaturating amounts of fatty acids [Ross, P., & Shrake, A. (1987) Abstracts of the 42nd Calorimetry Conference, University of Colorado, Boulder, CO].

Binding Sites↗
PubMed1988

Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820.

Laboratory rats and mice were used to investigate the hepatotoxicity caused by the cyclic heptapeptide (mol. wt 994) termed microcystin-LR. Microcystin-LR (also known as cyanoginosin-LR) is produced by the freshwater cyanobacterium (blue-green alga) M. aeruginosa strain PCC-7820. In time course histopathology studies with mice significant liver damage, with an absence of pulmonary emboli, were observed after 15 min. Pulmonary emboli did not appear until 1 hr. In rats, significant liver damage and the presence of occasional emboli were observed at 20 min. Pulmonary emboli did not contain fibrin nor appear life-threatening in any case and resembled the globular eosinophilic debris found in the liver sinusoids and central veins. Measurements of rat femoral arterial, jugular venous and hepatic portal venous blood pressures during the course of toxicity revealed a slowly declining arterial pressure and stable, normal venous pressures. Blood lactic acid levels rose in parallel with the fall in arterial pressure, a pattern typical of hemorrhagic shock. There was no indication of venous congestion that would accompany right heart failure. Isolated, perfused rat livers dosed with toxin showed rapid changes in the liver, including cessation of bile flow within 10 min and complete obliteration of normal lobular architecture within 60 min. No effect of the toxin was observed in isolated perfused rat heart. We conclude that in the mouse and rat, microcystin-LR is a potent, rapid-acting, direct hepatotoxin, with the immediate cause of death in acute toxicities being hemorrhagic shock secondary to massive hepatocellular necrosis and collapse of hepatic parenchyma.

Animals↗
PubMed1988

Isolated rat liver perfusion studies with cyclic heptapeptide toxins of Microcystis and Oscillatoria (freshwater cyanobacteria).

Isolated perfused rat livers were used to study the dose-dependent effects of three cyclic heptapeptide toxins isolated from Norwegian freshwater bloom samples containing Microcystis aeruginosa, Oscillatoria agardhii var. and Oscillatoria agardhii var. isothrix. The high pressure liquid chromatography (HPLC) purified toxins had an i.p. LD50 in the rat and mouse of approximately 50, 500 and 1000 micrograms/kg, respectively. Hepatic insult of the toxins at concentrations of 0.5-4.0 times the rat i.p. lethal dose were assessed by monitoring bile flow, accumulation of total protein in the perfusate, release of intracellular enzymes and histopathologic examination of perfused liver tissue. One hundred micrograms of Microcystis toxin produced cessation of bile flow during a 1 hr perfusion period, while the two Oscillatoria toxins required 1000 and 2000 micrograms of toxin, consistent with their lower LD50 values. Hepatic cell membranes remained intact during the perfusion since release of enzymes and proteins into the perfusate was similar for toxin treated and control livers, and histopathologic examination of Trypan Blue infused livers revealed exclusion of the dye from the intracellular compartment of the parenchyma. Histopathologic findings for all three toxins showed hepatocellular disassociation that increased with toxin concentration. At the ultrastructural level, all three toxins caused dose-dependent vesiculation of rough endoplasmic reticulum, formation of concentric whorls composed of rough-ER, mitochondrial swelling, large cytoplasmic vacuoles and altered bile canaliculi. These changes were similar to those found for previous in vivo studies using Microcystis cyclic heptapeptides from Scotland and Australia. The Oscillatoria toxins required five to ten times more toxin to produce similar effects as the Microcystis toxin. At the higher concentrations, the Oscillatoria toxins also caused a proliferation of smooth-ER. The isolated perfused rat liver was found to be a good model for studying the hepatocellular effects of different cyclic peptide toxins from cyanobacteria.

Animals↗
PubMed1988

Canonical formulation of linkage thermodynamics.

The canonical structure of the group of thermodynamic potentials obtained from the energy of a physico-chemical system removes any possible distinction between physical and chemical binding phenomena. Transformations of these potentials by means of Jacobians give linkage relations for equilibrium thermodynamics. Linkage matrices are introduced to explore the functional properties of a biological macromolecule. They provide a quantitative basis for a broader approach and understanding of generalized binding phenomena.

Carbon Monoxide↗
PubMed1988

Chemical oscillations in closed macromolecular systems.

A cycle of irreversible, first-order, autocatalytic reactions among different states of a polyfunctional macromolecule, subject to the conservation of mass, can display stable chemical oscillations. This introduces a class of nonlinear dynamic models for energy transduction in closed macromolecular systems.

Chemical Phenomena↗
PubMed1988

Binding capacity: cooperativity and buffering in biopolymers.

The group of linkage potentials resulting from the energy of a physicochemical system expressed per mol of a reference component, say a polyfunctional macromolecule, leads to the concept of binding capacity. This concept applies equally to both chemical and physical ligands and opens the way to consideration of higher-order linkage relationships. It provides a means of exploring the consequences of thermodynamic stability on generalized binding phenomena in biopolymers.

Biopolymers↗
PubMed1988

Allosteric equilibria in the binding of fibrinogen to platelets.

The binding of fibrinogen to platelets occurs according to the law of mass action. The platelet receptor binds reversibly a single fibrinogen molecule and undergoes a conformational transition between two allosteric states, T and R, that differ in their affinity for fibrinogen. The equilibrium between the two forms is shifted by ADP toward the R (high-affinity) state, thus promoting the aggregation process. This model opens the way to consideration of allosteric modulation of the binding of fibrinogen to its platelet receptor.

Adenosine Diphosphate↗