Structural similarities between hematoidin crystals and asteroid bodies: evidence of lipid composition

Hematoidin crystals (HC) are found in tissues where extravasated erythrocytes undergo degradation. Previous studies have determined that hematoidin is composed, in part, of a bilirubin-like pigment. In a previous study (Papadimitriou and Drachenberg, Ultrastruct. Pathol. 16, 413-421, 1992), we demonstrated that giant cell asteroid bodies (AB) are formed by membrane lipid bilayers. We evaluated three cases in which HC developed within splenic infarcts. The crystals were analyzed by light microscopy (LM), electron microscopy (EM), and X-ray microanalysis. A case of sarcoidosis with multiple epithelioid granulomas containing AB was studied for comparison. By LM the HC demonstrated intense, golden-color, fine threads, both intracellularly and extracellularly, in small and large clusters, and in radiating, star-shape patterns ranging in size from 2 to 200 microm. By EM the HC were composed of a core of empty clefts, consistent with dissolved lipids, suggestive of cholesterol crystals, and were surrounded by myelinoid membrane aggregates. The AB showed by LM significant morphological similarities with the intracellular HC. By EM, the AB were composed of a core of dense phospholipid bilayer tubes surrounded by a halo of myelinoid membranes. No accumulation of specific elements was found in either HC or AB by X-ray microanalysis. HC and AB show a similar star-shape morphology by both LM and EM. We postulate that this shape is due to the physicochemical properties of the accumulated lipids which originate from superfluous cell membranes created during cell fusion in the case of AB and after cellular (predominantly red cell) breakdown in the case of HC. The golden color of the HC likely results from adsorption of hydrophobic bilirubin-like pigments left over from erythrocyte breakdown into the accumulated lipids. Thus, this study shows two different (patho)physiological processes that lead to a markedly similar morphological end-product and provides further support to our proposed mechanism for AB formation.     

A study of the correlation between organic matrices and nanocomposite materials in oyster shell formation

Calcium carbonate minerals are an integral part of many organisms. These biogenic minerals are all of original size, shape and high strength, and they are quite different from those found in their abiotic precipitates. It has been accepted that the formation, morphological development and crystallography of the biocomposites are controlled by the intrinsic molecular recognition of macromolecules. In this study, with the analyses of X-ray diffraction and scanning electron microscopy of the texture of biogenic minerals in oyster shells, we noted that the intracrystalline proteins deliberately reduce the coherence lengths of biogenic crystals compared to synthetic ones, leading to more isotropy. In order to understand the exact nature of the controlled nucleation and growth, we investigated the changes in protein conformation in vivo from the mineral-specific layers using Fourier self-deconvolution and Gaussian curve-fitting techniques. And via in vitro assays, we studied the relation of such changes to biomineral phase and morphology. We showed that the shell proteins in vivo are in the higher structural ordered state, and beta-antiparallel structure was predominant in each shell layer. Also, as the shell undergoes a change of calcium carbonate polymorphs from aragonite to calcite, significant alterations of the protein conformation with the denaturing of alpha-helix and beta-structure in the aragonitic layer is induced. These results provide a relationship between the effects of conformational changes on the nanostructure of biocomposites and the necessity of new synthetic strategies.     

Rheological studies on the solubilization by the surfactant SDS of complexes between three acidic polysaccharides and an organic base chloride

Developments in the solubilization of complexes between the cationic polymer, poly(hexamethylenebiguanidinium chloride) (PHMBH⁺Cl^-) and acidic polysaccharides are reported. It was discovered that the anionic detergent sodium dodecyl sulphate (SDS) is an excellent solubilizer for these complexes, enabling several multi-component systems to be studied. SDS itself was shown to interact with PHMBH⁺CL^- to form a highly viscous solution. Maximum viscosity was obtained with a SDS : PHMBH⁺CL^- molar ratio of 15.6. SDS : PHMBH⁺Cl^- at this ratio served as a good solubilizer for the acidic polysaccharides (sodium alginate, sodium carboxymethyl cellulose, and xanthan), forming highly viscous fluids. The effect of temperature on the viscosity of these solutions was also examined.     

Interstitial fluid: exchange of macromolecules between plasma and skin interstitium

Fluid was collected from blisters developed by suction on the abdominal skin in ten normal volunteers. During the same study the transcapillary escape rate of intravenously injected 131I-albumin and 125I-IgG together with the accumulation of these tracers in the blister fluid was measured. The ratios between the concentrations of endogenous albumin, transferrin, IgG and alpha 2-macroglobulin in the blister fluid (Cb) and serum (Cs) correlated directly with the free diffusion coefficients indicating that the sieving properties of the vascular endothelium remained intact during the suction. The ratios of intravascular to total masses of the four endogenous proteins calculated from plasma volume, Cs, Cb and extracellular fluid volume determined with inulin and Cb were very similar to those obtained in long-term metabolic turnover studies. The ratio between the accumulated IgG and albumin tracers in the blister fluid (0.80) was identical with the Cb/Cs ratio between endogenous IgG and albumin (0.78) but higher than the ratio between the IgG and albumin escape rates from the total microvasculature (0.58). From the protein tracer determinations it cannot be definitely excluded that suction increases the microvascular escape rates. If the distribution volume of inulin equates that of albumin in steady-state it can, however, be concluded from the data given on the endogenous plasma protein, that blister fluid from the abdominal skin corresponds to average interstitial tissue fluid.     

Different regulation of hepatocyte behaviors between natural extracellular matrices and synthetic extracellular matrices by hepatocyte growth factor

The roles of growth factors and extracellular matrices (ECMs) in regulation of hepatocyte behaviors are very important for the establishment of liver-tissue engineering. Especially, collaboration between growth factors and ECMs is a big concern for liver-tissue engineering. In this study, the hepatocyte responses by hepatocyte growth factor (HGF) were compared between natural ECMs and a synthetic galactose-carrying polymer: poly(N-p-vinylbenzyl-4-O-beta-D-galactopyranosyl-D-gluconamide) (PVLA). Hepatocytes underwent proliferation on type I collagen- and fibronectin-coated surfaces in the presence of HGF, whereas hepatocytes formed spheroid on laminin-1-, PVLA-, and poly-L-lysine (PLL)-coated surfaces in the presence of HGF without the activation of proliferation. HGF accelerated ECM deposition, especially laminin-10/11, beneath the hepatocytes cultured on PVLA- and PLL-coated surfaces and the deposited laminin-10/11 activated integrin signaling to collaborate with HGF signaling. Therefore, the deposited ECM molecules should be focused to clear the mechanism of hepatocyte behaviors in the presence of HGF.     

Functionality and stereochemical design of silicon-containing polymers

Molecular design and precision synthesis of silicon-containing polymers are described. The low rotational barrier energy around the silicon-oxygen bond was taken advantage of in designing a selectively oxygen permeable membrane material and new side-chain liquid crystalline polymers. The low surface free energy of polysiloxane graft copolymers was utilized in surface modification of a film consisting of a blend. Syntheses of stereoregular and/or optically active silicon-containing polymers from optically active silicon compounds are presented as well.     

Structural and mechanical properties of the organic matrix layers of nacre

The type of nanostructure referred to in biomineralization as a mineral bridge has been directly observed and measured in the organic matrix layers of nacre by transmission electron microscopy and scanning electron microscopy. Statistical analysis provides the geometric characteristics and a distribution law of the mineral bridges in the organic matrix layers. Experiments reveal that the nanostructures significantly influences the mechanical properties of the organic matrix layers. In addition, the mechanical analysis illustrates the effects of the nanostructures on the behaviors of the organic matrix layers, and the analytical results explain the corresponding experimental phenomena fairly well. The present study shows that the mineral bridges play a key role in the mechanical performances of the organic matrix layers of nacre. The results obtained provide a guide to the interfacial design of synthetic materials.     

Presence of covalent bonds between immune deposits and other macromolecules in murine renal glomeruli

Microscopic studies have suggested that immune deposits persist for a long time in subepithelial areas of renal glomeruli in human diseases and in experimental models. This study showed quantitatively that in an experimental murine model radiolabelled antibodies in subepithelial immune deposits remained constant for 9 months at about 3 μg/mouse. The extraction of these antibodies was incomplete with 1% SDS at 8 months after immune deposit formation. Furthermore, in the extracted material some antibodies were covalently bound to other molecules. This study demonstrates that covalent bond formation contributes to the persistence of immune deposits in renal glomeruli.     

Association between immunity to collagen and the pathology of extracellular matrices

In a first part, the data of immunogenicity of collagen type II and type IV in physiopathology of extracellular matrices as cartilage and basement membrane, are reviewed. However, in the second part, this conclusion will be examined by basing on the knowledge of the nature of specific sites of these collagens and the variable or non specific humoral immune response towards these collagens in human diseases.     

Implicating causal relations between cellular function and learning behavior

Learning in the nudibranch mollusc Hermissenda shows many features of vertebrate associative conditioning. Pairings of light and rotation produce conditioned suppression of phototaxis, which is retained for days, shows savings, extinction, contingency sensitivity, and, recently, temporal specificity. In addition, specific features of the behavior have been shown to undergo classical Pavlovian conditioning. Extensive analysis of the neural networks mediating the flow of visual and graviceptive information have demonstrated convergent pathways at specific cellular loci. These cells are critically implicated for a primary role in the conditioned modifications of behavior. A variety of experimental approaches consistently support the proposal that reductions of specific K+ currents in the Type B photoreceptor soma play a causal role for several different behavioral expressions of the conditioning. In this article, we review several of these behaviors to show how the demonstrated close temporal correspondence of cellular and behavioral functions further implicates certain causal relations. For example, studies of the shadow withdrawal behavior of Hermissenda suggest a causal relation between the long-lasting depolarization of the Type B photoreceptor and the animal's reduced ability to turn towards the light at light/dark boundaries. Whereas the shadow response corresponded to cellular events at the end of a light step, responses to the onset of light or rotation were largely unexplored. By using a different approach, we identified behavioral responses during the first few seconds of stimulation with light and rotation. These responses, for which Pavlovian conditioning was demonstrated, correspond closely in time to known cellular correlates.(ABSTRACT TRUNCATED AT 250 WORDS)     

True and false agreement relations between 2 qualitative tests

The respective effectiveness of two qualitative tests is usually compared by their results when applied to a same specimen or subject. The results reported in a fourfold table show coincident numbers of double positive and double negative results. That straight concordance is fallacious, including the chance coincidences. Test Kappa measures the true agreement, without the chance coincidences. Kappa value may be compared to a maximum value of agreement depending on the marginal results of the fourfold table. As a matter of fact, the test Kappa is a non parametric correlation function comparable to the non parametric correlation coefficient Phi computed from the value of the chi square test.     

Intrinsic functional relations between human cerebral cortex and thalamus

The brain is active even in the absence of explicit stimuli or overt responses. This activity is highly correlated within specific networks of the cerebral cortex when assessed with resting-state functional magnetic resonance imaging (fMRI) blood oxygen level–dependent (BOLD) imaging. The role of the thalamus in this intrinsic activity is unknown despite its critical role in the function of the cerebral cortex. Here we mapped correlations in resting-state activity between the human thalamus and the cerebral cortex in adult humans using fMRI BOLD imaging. Based on this functional measure of intrinsic brain activity we partitioned the thalamus into nuclear groups that correspond well with postmortem human histology and connectional anatomy inferred from nonhuman primates. This structure/function correspondence in resting-state activity was strongest between each cerebral hemisphere and its ipsilateral thalamus. However, each hemisphere was also strongly correlated with the contralateral thalamus, a pattern that is not attributable to known thalamocortical monosynaptic connections. These results extend our understanding of the intrinsic network organization of the human brain to the thalamus and highlight the potential of resting-state fMRI BOLD imaging to elucidate thalamocortical relationships.     

Phase relations between carotid pressure and ongoing electrocortical activity

The behavioral significance of changes in the cardiovascular system has been a major source of controversy in psychophysiology. In view of this, it is surprising that so few studies have examined the relationship between cardiac events and electrocortical (EEG) activity in human subjects. In the present study, this relationship was examined by comparing phase, amplitude and frequency of EEG activity sampled during systolic and diastolic pressure recorded from the carotid artery of resting subjects. The results indicated that rhythmic oscillations of the EEG (particularly those in the alpha range) were time-locked to the carotid pressure wave, and EEG samples taken during systolic and diastolic pressure were distinctly out of phase. In addition, EEG activity sampled during systolic pressure was comprised of slower frequencies than EEG activity sampled during diastolic pressure. It was suggested that the relationship between cardiac events and behavior may be mediated in part by influences of the cardiovascular system on electrocortical rhythms.     

Study of relations between arterial oscillation period and heart rate

Summary This study was performed to determine the relationship between variations of arterial cross-section and cardiac period. Relative section variations were recorded by impedance rheography. In 176 anesthetized adult mongrel dogs, aortic and femoral rheograms, femoral pressure, and ECG were recorded. The cardiac period (Tc) and the interval between the systolic and the dicrotic wave, i.e., the arterial intrinsic period (Ta), were measured and related to each other (Tc/Ta ratio). In 125 dogs, the dicrotic wave appeared spontaneously. In these cases Tc/Ta 1.98±0.16. In 51 dogs, no dicrotic wave appeared spontaneously. Lenghtening of cardiac period was obtained in 25 of these dogs by vagus stimulation. As related to the cardiac period before vagal stimulation Tc/Ta was then 0.98±0.08. In the remaining 26 dogs, such a lengthening was obtained by inducing a premature ventricular depolarization. In this group, Tc/Ta was 1.00±0.03. The results of the present study suggest that a constant adaptation exists between ventricular ejection and arterial dynamics. The physiologic implications are discussed.Supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, and Délégation Générale à la Recherche Scientifique et Technique (DGRST)