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Thermodynamic studies of the collagen-like region of human subcomponent C1q. A water-containing structural model.

Thermal transitions of Clq were investigated by methods of differential scanning calorimetry, circular dichroism and fluorescence. The melting curves of Clq display two pronounced heat absorption peaks with enables determination of the thermodynamic parameters characterizing each transition. The low temperature peak was assigned to melting of the Clq collagenous part. Analysis of the data has revealed unusual, as compared with the monomeric collagen molecules, thermodynamic features of the Clq collagenous part: (1) higher thermal stability strongly dependent on pH; (2) less linear co-operative regions; and (3) a noticeable change in the partial specific heat capacity (delta Cp) in contrast to both the monomeric collagen and the collagen fibrils. This unusually large delta Cp value suggested a conclusion that the fibril-like endpiece of Clq may have a cavity filled with ice-like ordered water molecules.

Calorimetry, Differential Scanning↗

Structured modeling and simulation of oxygen transport to hybridoma cell in a suspension culture: theoretical analysis.

The importance of the consideration of micro-anatomical and cytological observation for the oxygen utilization by hybridoma cells are emphasized. Tumor cells have considerably lower content of mitochondria and that cells metabolize much of their carbon source by anaerobic pathway, therefore, consumes much less oxygen. Because of the fact that hybridoma cells are derived from a myeloma cell, which is a type of tumor cell, there may be possibility that the oxygen demand could be closely related to mitochondrial content of the resulting cell. Possible correlation between the optimum DOT and mitochondrial content of the hybridoma cells is hypothesized. By simulating oxygen transport inside of a single hybridoma cells for the cases of three different mitochondrial contents, possible differences in the optimum DOT according to the mitochondrial contents were studied and the results reported.

Animals↗

Experimental neurotoxicity of the anorectic fenfluramine. I. A fine structural model for cerebral lysosomal storage and neuroglial reaction.

Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8-19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic "reactive microglia" were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.

Animals↗

Congenital genetic murine (ch) hydrocephalus. A structural model of cellular dysplasia and disorganization with the molecular locus of deficient proteoglycan synthesis.

The recessively inherited ch hydrocephalic mouse has been sporadically investigated over the past 40 years as a genetic murine model for congenital hydrocephalus. Since central nervous system anomalies are commonly associated with congenital anomalies in the musculoskeletal and urogenital systems, and since congenital hydrocephalus is also associated with other developmental abnormalities, an understanding of the pathophysiology at the cellular and molecular levels of the genetic defects of this hydrocephalic murine model has application to related human disorders associated with hydrocephalus. A unifying hypothesis is presented that can interrelate the multisystem developmental abnormalities. While the basic cellular defect is a failure of mesenchymal differentiation, the molecular locus is a synthetic defect in the production of the chondroitin sulfate proteoglycan. The primary end results of defective proteoglycan synthesis at a multiorgan-multisystem level includes chondrodysplasia, renal dysplasia, failure of endochondral ossification and gonadal development, and defective development of the adrenal medulla and the sympathetic ganglia. The development of the severe, communicating, congenital hydrocephalus in the ch mouse may be either a primary or secondary manifestation of the mesenchymal maldifferentiation.

Animals↗

Structural models of captivity trauma, resilience, and trauma response among former prisoners of war 20 to 40 years after release.

Long-term responses to captivity trauma were measured in a national sample of American former prisoners of war. Their responses included negative affect, positive affect, and somatic symptoms as assessed by the Cornell Medical Index in 1967 and the Center for Epidemiological Study Depression Scale in 1985. These responses were strongly associated with captivity trauma (as indexed by captivity weight loss, torture, and disease) and resilience (as indexed by age and education at capture). Symptoms reported in 1967 were related to symptoms reported in 1985, suggesting symptom stability. These results are consistent with a model of trauma response that incorporates both trauma exposure and individual resilience. The findings are interpreted within a theoretical view of trauma response as adaptive when viewed from an evolutionary perspective.

Aged↗

Body image and eating restraint: a structural modeling analysis.

Body-image disturbance and its link with eating behaviors are poorly understood and controversial phenomena. The model proposed by Cash (1996) is perhaps the most unified current attempt to analyze this link. Its central features are a separation of historical and proximal influences and the link between body image emotions and adjustive, emotion regulating actions. This model, however, and in particular the link between body dissatisfaction and eating restraint have not been empirically tested. A series of different causal models for directly observed variables (LISREL 7) have therefore been used to determine the soundness of this link in a study of 130 female undergraduates. The goodness-of-fit of the models suggests that a causal link exists. It is clear that body image therapy should be combined with current treatments for obesity and eating disorders.

Adult↗

The mechanical behaviour of chondrocytes predicted with a micro-structural model of articular cartilage.

The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.

Animals↗

Nicotinic acetylcholine receptor: a structural model for alpha-subunit peptide 188-201, the putative binding site for cholinergic agents.

A peptide corresponding to amino acid sequence 188-201 of the alpha-subunit of Torpedo AChR binds alpha-Bgtx. The S-S bridge between Cys 192 and 193 is essential for the binding as Tyr in position 189. The same sequence 188-201 corresponding to human AChR, which instead of Tyr has a Thr in position 189, binds alpha-Bgtx with a much lower efficiency. Monoclonal antibodies raised against Torpedo peptide 188-201 recognize Torpedo AChR and antibodies against Torpedo AChR recognize peptide 188-201 indicating that the synthetic peptide and the corresponding sequence in the native molecule share some immunological epitopes. With computer graphics and energy refinement a molecular model of this peptide has been elaborated.

Amino Acid Sequence↗

Cycles in nonlinear age-structured models. I. Renewal equations.

A variety of density-dependent population models can be described by nonlinear renewal equations. This paper develops analytical tools for such models to study the sustained population cycles which arise by bifurcation. The results obtained describe explicitly the direction of bifurcation, and the period, form, and dynamic stability of sustained cycles. The results are illustrated by application to a cohort-controlled model of human populations which has been proposed as a formalization of the Easterlin effect.

Age Factors↗