China
Africa
Explore chapters and articles related to this topic
Primary Stress Damage of the Heart
Published in Felix Z. Meerson, Alexander V. Galkin, Adaptive Protection of The Heart: Protecting Against Stress and Ischemic Damage, 2019
Felix Z. Meerson, Alexander V. Galkin
The thermodynamic parameters of Na,K ATPase heat inactivation in Table 15 reveal two basic facts: the lower activation energy and a smaller change in entropy during denaturation of the enzyme from stress animals. In essence they both mean that the stress itself brings the Na,K ATPase protein-lipid complex closer to the denatured state; these changes are prevented by prior suppression of free-radical lipid oxidation.
Red Cells Containing Unstable Hemoglobin Variants
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
The studies of Privalov and co-workers63 have demonstrated that myoglobin, and presumably all globular proteins, denature in an almost all-or-none phenomena that can be approximated well by a two-state transition. In addition, this process results in a significant increase in heat capacity. The process of denaturation of hemoglobin can be expected to be a cooperative phenomena and once it begins it will most likely end in the denatured state. Privalov et al.64 have recently studies the cold denaturation of myoglobin (low pH) and concluded that this phenomena is probably the consequence of the decrease in hydrophobic interactions upon cooling (the negative temperature coefficient of the hydrophobic interactions which are a mixture of a water-ordering effect by the nonpolar side chains and the van der Waals’ contacts between them). Heat denaturation, in this scheme, will be secondary to an increase in the dissipatory forces with temperature that is faster and the increase in hydrophobic interactions. Hence proteins are stable in the limited range in which hydrophobic interactions are strong enough and dissipative forces are too weak.
The High Mobility Group (HMG) Proteins
Published in Lubomir S. Hnilica, Chromosomal Nonhistone Proteins, 2018
The HMG proteins prepared by these methods are recovered in a denatured state due to the exposure to acids. This is not a problem with HMG14 and 17 (being random coil proteins anyway), but HMG1 and 2 proteins may be irreversibly affected since highly they are proteins which have highly ordered structures (see Section III. C). Thus a method has been developed recently for isolating nondenatured proteins by avoiding the use of acids.13 In this method the HMG proteins are extracted from chromatin with 0.35 M NaCl and the extract is fractionated by phosphocellulose chromatography at pH 7.5.
A thermoelastic deformation model of tissue contraction during thermal ablation
Published in International Journal of Hyperthermia, 2018
Chang Sub Park, Cong Liu, Sheldon K. Hall, Stephen J. Payne
Tissue heating leads to an increase in the forward and backward reaction rates between the native and unfolded states. The reaction rates increase at different amounts with increasing temperature. An overall forward reaction rate occurs above a threshold temperature leading to protein changing from the native to the unfolded state. Since protein length decreases along the denaturation process, this leads to an initial tissue contraction. This is followed by proteins changing from the unfolded to the denatured state causing further contraction. Returning the temperature back to baseline causes an overall backward reaction rate between the native and unfolded state, which is significantly greater than the forward reaction rate from the unfolded to the denatured state. As a result, any unfolded protein left will return back to its native state, causing a recovery in tissue contraction. The simulation results, however, found this to be small (around 2% depending on applicator temperature) as most of the protein had already progressed to the denatured state. Tissue contraction was also observed in areas outside the heated region, thus further highlighting the importance of tissue displacements during hyperthermal ablation therapies. Note that the largest contractions were not observed where the tissue temperature was at its highest.
Engineering T cell response to cancer antigens by choice of focal therapeutic conditions
Published in International Journal of Hyperthermia, 2019
Qi Shao, Stephen O'Flanagan, Tiffany Lam, Priyatanu Roy, Francisco Pelaez, Brandon J Burbach, Samira M Azarin, Yoji Shimizu, John C Bischof
In this study of cancer-associated adaptive immune response, the release of both antigens and ‘danger signal’ (or damage-associated molecular pattern molecules, DAMPs [55]) can be controlled by the type of focal therapeutic conditions used to destroy the cancer cells. Antigens dictate the generation of antigen-specific T cells while the ‘danger signal’ modulates the antigen processing and presentation of the APCs and the priming and activation of T cells. We further show that these differences can be exploited to promote enhanced CD8 T cell activation, as summarized in Figure 7. This study demonstrates that while all focal therapies can cause cell death, the ‘quantity’ (i.e., amount) and ‘quality’ (i.e., physiochemical conditions) of protein released from cancer cells and the ensuing priming of the immune system can differ dramatically. In general, more cells will proportionally release a larger quantity of protein and specific antigen for a specific focal therapeutic condition. Our data also support the concept that greater protein and antigen availability favors increased antigen-specific T cell activation and proliferation. However, when the T cell proliferation response was normalized to protein quantity in the lysate for specific focal therapeutic conditions, clear differences in T cell response were noted, which favored IRE over Cryo and Heat. For instance, while the presence of protein in the lysate is required, there are vastly different T cell responses from each focal therapeutic condition for a given amount of protein. This then suggests a further ‘quality’ of the protein in the lysates is necessary to promote T cell response. To prove this concept of quality we further measured: (1) native vs. denatured state of released protein, (2) presence of known B16 antigen TRP-2 in the lysate.
Excipients in parenteral formulations: selection considerations and effective utilization with small molecules and biologics
Published in Drug Development and Industrial Pharmacy, 2018
Bindhu Madhavi Rayaprolu, Jonathan J. Strawser, Gopal Anyarambhatla
Protein stabilizing excipients are added to the formulation to prevent aggregation, destabilization of the denatured state, direct binding to the protein, during isolation and purification and drying, preferential exclusion in which the excipient is excluded from the protein surface preventing the unfavorable excipient-protein interactions. Such stabilizers include sugars, buffering agents, antioxidants, surfactants, amino acids and amines, salts, and polysaccharides.