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We have shown a basic biophysical difference between clinically similar hand injuries and suggest that some rotary lawn mower injuries more closely resemble high-velocity missile injuries. A treatment protocol is suggested.
The application of some physical concepts is described to explain the inherent insensitivity of 99Tc(m)-red blood cell (RBC) and 99Tc(m)-human serum albumin (HSA) in the detection of gastrointestinal bleeding and protein-losing enteropathy (PLE), respectively. Inferences drawn from the laws of radioactive decay, partition physics, hydrodynamics and electrostatic forces have been used to suggest that the clearance pattern, size and charge of radiopharmaceuticals, and the viscosity of the medium, affect the sensitivity of these tests. As the outflow from gastrointestinal lesions is non-specific, other labelled macromolecules can be used instead of RBCs or HSA. Based on biophysical concepts, we suggest that chargeless macromolecules in the size range 5-50 nm are superior to the conventional agents used for this purpose.
Affibodies are a novel class of binding proteins selected from phagemid libraries of the Z domain from staphylococcal protein A. The Z(SPA-1) affibody was selected as a binder to protein A, and it binds the parental Z domain with micromolar affinity. In earlier work we determined the structure of the Z:Z(SPA-1) complex and noted that Z(SPA-1) in the free state exhibits several properties characteristic of a molten globule. Here we present a more detailed biophysical investigation of Z(SPA-1) and four Z(SPA-1) mutants with the objective to understand these properties. The characterization includes thermal and chemical denaturation profiles, ANS binding assays, size exclusion chromatography, isothermal titration calorimetry, and an investigation of structure and dynamics by NMR. The NMR characterization of Z(SPA-1) was facilitated by the finding that trimethylamine N-oxide (TMAO) stabilizes the molten globule conformation in favor of the fully unfolded state. All data taken together lead us to conclude the following: (1) The topology of the molten globule conformation of free Z(SPA-1) is similar to that of the fully folded structure in the Z-bound state; (2) the extensive mutations in helices 1 and 2 destabilize these without affecting the intrinsic stability of helix 3; (3) stabilization and reduced aggregation can be achieved by replacing mutated residues in Z(SPA-1) with the corresponding wild-type Z residues. This stabilization is better correlated to changes in helix propensity than to an expected increase in polar versus nonpolar surface area of the fully folded state.
An artificial pulmonary surfactant prepared from chloroform-methanol extract of bovine pulmonary surfactant (surfactant TA) has been shown to be effective in both the prevention and the treatment of respiratory distress syndrome in premature babies. Recently, two types of protein-free totally synthetic surfactants, artificial lung expanding compound (ALEC) and Exosurf, have been evaluated in clinical trials of surfactant therapy. Artificial lung expanding compound was used initially as a dry powder, but is now prepared as a crystalline suspension in saline at 4 degrees C. In this study we compared the biophysical properties of three different forms of ALEC (dry powder, crystalline suspension at 4 degrees C and 37 degrees C), Exosurf and surfactant TA (Surfacten) using a modified Wilhelmy surface balance and a pulsating bubble surfactometer. Surface activity of a crystalline suspension of ALEC in cold saline was no better than the dry powder of ALEC. Surfactant activity of ALEC was improved by addition of hydrophobic surfactant protein B and C (SP-B, SP-C) which are important constituents of surfactant TA. Surface properties of ALEC in any form and Exosurf were not superior to those of surfactant TA. These results suggest that a surfactant which contains SP-B and SP-C does not necessarily have to be dry or crystalline for an effective exogenous surfactant.
Sensitive skin has been described as a skin type showing higher reactivity than normal skin and developing exaggerated reactions when exposed to external factors. The stinging test, performed by applying lactic acid to the nasolabial fold and evaluating the intensity of subjective symptoms, is widely accepted as a marker of sensitivity and employed for the selection of subjects experiencing invisible cutaneous irritation. However, this test is based on self-perceived assessment and lacks objectivity. In order to contribute to the finding of objective descriptors, we assessed baseline biophysical parameters in subjects with sensitive skin by means of transepidermal water loss (TEWL), capacitance, pH, sebum and skin colour measurements, and compared the data with those obtained in normal subjects, also correlating the results with those of clinical assessments and functional tests. Subjects with sensitive skin showed a trend towards higher scores at all assessment times both for the stinging and the washing test. The skin of sensitive subjects was described as less supple, less hydrated and more erythematous and telangiectatic with respect to the skin of normal subjects. A trend towards an increase in TEWL, pH and colorimetric a* values, and a decrease in capacitance, sebum and colorimetric L* values on the face of subjects with sensitive skin was observable. However, significances were only present for capacitance and a* values. Thus, alterations of baseline capacitance values indicate the tendency to barrier impairment and support the view that skin hyperreactivity to water-soluble irritants is induced by a greater amount of irritants absorbed, whereas the increase in the erythema parameter shows that cutaneous vascular hyperreactivity in subjects with sensitive skin also corresponds to baseline vasodilation.
Hemolysis induced by 1.9-MHz ultrasound in 0.5% suspensions of canine erythrocytes with 3.7-microns-diam micropore-trapped gas bodies was investigated for a variety of biophysical conditions. For isotonic media, hemolysis increased with exposure duration (4-64 min) but did not greatly change with exposure temperature (15, 25, 37, and 48 degrees C), or prior heat treatment (48 or 50 degrees C for 30 min). The temperature results were especially interesting because increased temperatures might have been expected to increase the sensitivity of the cells to the ultrasonically activated gas bodies. Variations in osmolarity (180, 290, or 580 mOsm) had little influence on the results. Increasing the viscosity (0.7, 2.2, 2.3, or 4.2 cP) of the medium decreased the effect, and this did not seem to depend on the molecular weight of the dextran additive (9400 or 250,000). A medium with elevated mass density (1.12 g/cm3) seemed to increase the effectiveness of the exposures. This condition eliminated the density difference between the cells and the medium, and might have been expected to reduce the effectiveness of the exposures, because the radiation force, which theoretically gathers cells to the gas bodies, is minimized for such conditions. This information should aid in developing refinements to the theoretical understanding of low-intensity ultrasonic bioeffects.
Phytases (myo-inositol hexakisphosphate phosphohydrolases) are found naturally in plants and microorganisms, particularly fungi. Interest in these enzymes has been stimulated by the fact that phytase supplements increase the availability of phosphorus in pig and poultry feed and thereby reduce environmental pollution due to excess phosphate excretion in areas where there is intensive livestock production. The wild-type phytases from six different fungi, Aspergillus niger, Aspergillus terreus, Aspergillus fumigatus, Emericella nidulans, Myceliophthora thermophila, and Talaromyces thermophilus, were overexpressed in either filamentous fungi or yeasts and purified, and their biophysical properties were compared with those of a phytase from Escherichia coli. All of the phytases examined are monomeric proteins. While E. coli phytase is a nonglycosylated enzyme, the glycosylation patterns of the fungal phytases proved to be highly variable, differing for individual phytases, for a given phytase produced in different expression systems, and for individual batches of a given phytase produced in a particular expression system. Whereas the extents of glycosylation were moderate when the fungal phytases were expressed in filamentous fungi, they were excessive when the phytases were expressed in yeasts. However, the different extents of glycosylation had no effect on the specific activity, the thermostability, or the refolding properties of individual phytases. When expressed in A. niger, several fungal phytases were susceptible to limited proteolysis by proteases present in the culture supernatant. N-terminal sequencing of the fragments revealed that cleavage invariably occurred at exposed loops on the surface of the molecule. Site-directed mutagenesis of A. fumigatus and E. nidulans phytases at the cleavage sites yielded mutants that were considerably more resistant to proteolytic attack. Therefore, engineering of exposed surface loops may be a strategy for improving phytase stability during feed processing and in the digestive tract.
McCombs, Robert M. (Baylor University College of Medicine, Houston, Tex.), Matilda Benyesh-Melnick, and Jean P. Brunschwig. Biophysical studies of vesicular stomatitis virus: J. Bacteriol. 91:803-812. 1966.-The infectivity and morphology of vesicular stomatitis virus (VSV) were studied after density gradient centrifugation in cesium chloride (CsCI), potassium tartrate (KT), and sucrose. Centrifugation in CsCl revealed two equally infectious bands corresponding to densities of 1.19 and 1.22 g/ml, and a third (density, 1.26 g/ml) band of low infectivity. Two bands (densities of 1.16 and 1.18 g/ml) were observed in the KT gradient, in which the lighter band contained most of the infectivity. Centrifugation in sucrose resulted in a single broad infectious band (density, 1.16 g/ml). The typical rod-shaped VSV particles were found mainly in the lighter bands obtained in CsCl (1.19 g/ml) and KT (1.16 g/ml) and in the single sucrose gradient band (1.16 g/ml). Bent particles equally as infectious as the rod-shaped particles were a constant finding in the CsCl preparations, and were observed mainly in the second band (density, 1.19 g). Numerous strands 15mmu wide were found in the third CsCl (density, 1.26 g/ml) and the second KT (1.18 g/ml) bands. Similar strands could be liberated from VSV particles after treatment with deoxycholate. Internal transverse striations were found to be a regular feature of VSV particles examined with the pseudoreplication negative-staining technique. For crude virus stocks, the physical particle-to-infectivity ratio ranged from 73 to 194. Several morphological similarities between VSV and myxoviruses were observed, including 10 mmu surface projections, pleomorphic morphological forms, and 15 mmu seemingly nucleoprotein strands.
Forsyth, Ben R. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), Helen V. Coates, and Robert M. Chanock. Biophysical studies of respiratory syncytial virus. II. Identification of two soluble complement-fixing antigens of respiratory syncytial virus. J. Bacteriol. 91:1270-1276. 1966.-Column chromatography of concentrated preparations was used to separate two antigenic components from the "soluble complement-fixing (CF) antigen" of respiratory syncytial (RS) virus. These antigens, designated antigen A and antigen B, stimulated homologous but not heterologous CF antibodies. Only antigen A stimulated the production of neutralizing antibody in guinea pigs. There was a dissociation between the CF and neutralizing antibody responses of guinea pigs immunized with antigen A. The two antigens were shown to have different molecular size, density, and sensitivity to lipolytic agents. Both antigens appeared to be components of the RS viral particle. Serological studies demonstrated that both antigens were formed during RS virus infection of children and adults.
OBJECTIVE: To evaluate the role of biophysical response of the coarcted segment to balloon dilatation in the causation of aortic recoarctation. SETTING: Tertiary care centre/university hospital. DESIGN: Retrospective case series. METHODS: Records of 67 consecutive infants and children undergoing balloon angioplasty of native aortic coarctations were examined for an 8.7 year period ending September 1993. At 12 months (median) follow up catheterisation, 15 (25%) of 59 children developed recoarctation, defined as a gradient > 20 mm Hg. Stretch (balloon circumference--preballoon coarcted segment circumference/preballoon coarcted segment circumference), gain (postballoon coarcted segment circumference--preballoon coarcted segment circumference), and recoil (balloon circumference--postballoon coarcted segment circumference) were calculated from measurements obtained from cineangiograms performed before and immediately after balloon dilatation. RESULTS: The stretch in 44 children without recoarctation (2.18 (1.23)) was similar (p > 0.1) to that in 15 children with recoarctation (1.90 (0.65)), implying that similar balloon dilating stretch was applied in both groups. Greater gain (p < 0.05) was observed in the group without recoarctation (8.8 (8.0) mm) than in the recoarctation group (5.7 (2.7) mm) but this was not substantiated in the infant population. However, the recoil was greater (p < 0.001) in the group without recoarctation (5.1 (4.3) mm) than in the recoarctation group (2.1 (1.1) mm); this was also true in the infant group. CONCLUSIONS: Greater recoil in the patients without recoarctation implies preservation of intact elastic tissue in the coarcted segment. In the recoarctation group, with less recoil, the elastic properties may not have been preserved, thereby causing recoarctation. There might be a more severe degree of cystic medial necrosis in the recoarctation group than in the no recoarctation group. This needs confirmation in future studies.
In this issue, Lee et al. report the experimental temperature-dependence of the unzipping force for two natural DNA sequences. For both sequences, the curves show an anomaly at temperatures around 40 degrees C. In this brief contribution, we stress that the anomaly is not easily explained within the established theoretical models for the biophysics of DNA. As this puzzle questions our basic understanding of DNA, it must be resolved, most likely by a combination of additional experiments and new theoretical work.
Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
Recent meta-analyses have shown that the effects of climate change are detectable and significant in their magnitude, but these studies have emphasized the utility of looking for large-scale patterns without necessarily understanding the mechanisms underlying these changes. Using a series of case studies, we explore the potential pitfalls when one fails to incorporate aspects of physiological performance when predicting the consequences of climate change on biotic communities. We argue that by considering the mechanistic details of physiological performance within the context of biophysical ecology (engineering methods of heat, mass and momentum exchange applied to biological systems), such approaches will be better poised to predict where and when the impacts of climate change will most likely occur.
Patients with severe acute respiratory distress syndrome who die usually succumb to multiorgan failure as opposed to hypoxia. Despite appropriate resuscitation, some patients' symptoms persist on a downward spiral, apparently propagated by an uncontained systemic inflammatory response. This phenomenon is not well understood. However, a novel hypothesis to explain this observation proposes that it is related to the life-saving ventilatory support used to treat the respiratory failure. According to this hypothesis, mechanical ventilation per se, by altering both the magnitude and the pattern of lung stretch, can cause changes in gene expression and/or cellular metabolism that ultimately can lead to the development of an overwhelming inflammatory response-even in the absence of overt structural damage. This mechanism of injury has been termed biotrauma. In this review we explore the biotrauma hypothesis, the causal relationship between biophysical injury and organ failure, and its implications for the future therapy and management of critically ill patients.
Large-conductance Ca(2+)-activated potassium (BK) channels are composed of pore-forming alpha-subunits and auxiliary beta-subunits. The alpha-subunits are widely expressed in many cell types, whereas the beta-subunits are more tissue specific and influence diverse aspects of channel function. In the current study, we identified the presence of the smooth muscle-specific beta1-subunit in murine colonic tissue using Western blotting. The native beta1-subunits migrated in SDS-PAGE as two molecular mass bands. Enzymatic removal of N-linked glycosylations from the beta1-subunit resulted in a single band that migrated at a lower molecular mass than the native beta1-subunit bands, suggesting that the native beta1-subunit exists in either a core glycosylated or highly glycosylated form. We investigated the functional consequence of deglycosylating the beta1-subunit during inside-out single-channel recordings. During inside-out single-channel recordings, with N-glycosidase F in the pipette solution, the open probability (P(o)) and mean open time of BK channels increased in a time-dependent manner. Deglycosylation of BK channels did not affect the conductance but shifted the steady-state voltage of activation toward more positive potentials without affecting slope when Ca(2+) concentration was <1 microM. Treatment of myocytes lacking the beta1-subunits of the BK channel with N-glycosidase F had no effect. These data suggest that glycosylations on the beta1-subunit in smooth muscle cells can modify the biophysical properties of BK channels.
Pulmonary surfactant has two distinct functions within the lung: reduction of surface tension at the air-liquid interface and participation in innate host defense. Both functions are dependent on surfactant-associated proteins. Pseudomonas aeruginosa is primarily responsible for respiratory dysfunction and death in cystic fibrosis patients and is also a leading pathogen in nosocomial pneumonia. P. aeruginosa secretes a number of proteases that contribute to its virulence. We hypothesized that P. aeruginosa protease IV degrades surfactant proteins and results in a reduction in pulmonary surfactant host defense and biophysical functions. Protease IV was isolated from cultured supernatant of P. aeruginosa by gel chromatography. Incubation of cell-free bronchoalveolar lavage fluid with protease IV resulted in degradation of surfactant proteins (SP)-A, -D, and -B. SPs were degraded in a time- and dose-dependent fashion by protease IV, and degradation was inhibited by the trypsin-like serine protease inhibitor Nalpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK). Degradation by protease IV inhibited SP-A- and SP-D-mediated bacterial aggregation and uptake by macrophages. Surfactant treated with protease IV was unable to reduce surface tension as effectively as untreated surfactant, and this effect was inhibited by TLCK. We speculate that protease IV may be an important contributing factor to the development and propagation of acute lung injury associated with P. aeruginosa via loss of surfactant function within the lung.
We evaluated the changes in plasma membrane composition, biophysical properties, and morphology of pulmonary endothelial cells in anesthetized rabbits receiving 0.5 ml. kg(-1). min(-1) saline infusion for 180 min, causing mild interstitial edema. Plasma membrane fractions were obtained from lung homogenates with gradient centrifugation, allowing a sixfold enrichment in caveolin-1. In edematous lungs, cholesterol content and phospholipidic phosphorus increased by 15 and 40%, respectively. These data correlated with morphometric analysis of lungs fixed in situ by vascular perfusion with 2.5% glutaraldehyde, suggesting a relative increase in surface of luminal to interstitial front of the capillary endothelial cells, due to a convoluted luminal profile. In edematous lungs, the fraction of double-bound fatty acids increased in membrane lipids; moreover, the phosphatidylcholine/phosphatidylethanolamine and the cholesterol/phospholipid ratios decreased. These changes were consistent with the increase in fluorescence anisotropy of plasma membrane, indicating an increase in its fluidity. Data suggest that mechanical stimuli elicited by a modest (approximately 4%) increase in extravascular water cause marked changes in plasma membranes that may be of relevance in signal transduction and endothelial cell activation.
Amiloride-sensitive Na(+) channels, present in fetal and adult alveolar epithelial type II (ATII) cells, play a critical role in the reabsorption of fetal fluid shortly after birth and in limiting the extent of alveolar edema across the adult lung. Because of the difficulty in isolating and culturing ATII cells, there is considerable interest in characterizing the properties of ion channels and their response to injury of ATII cell-like cell lines such as A549 that derive from a human alveolar cell carcinoma. A549 cells were shown to contain alpha-, beta-, and gamma-epithelial Na(+) channel mRNAs. In the whole cell mode of the patch-clamp technique (bath, 145 mM Na(+); pipette, 145 mM K(+)), A549 cells exhibited inward Na(+) currents reversibly inhibited by amiloride, with an inhibition constant of 0.83 microM. Ion substitution studies showed that these channels were moderately selective for Na(+) (Na(+)-to-K(+) permeability ratio = 6:1). Inward Na(+) currents were activated by forskolin (10 microM) and inhibited by nitric oxide (300 nM) and cGMP. Recordings in cell-attached mode revealed the presence of an amiloride-sensitive Na(+) channel with a unitary conductance of 8.6 +/- 0.04 (SE) pS. Channel activity was increased by forskolin and decreased by nitric oxide and the cGMP analog 8-bromo-cGMP. These data demonstrate that A549 cells contain amiloride-sensitive Na(+) channels with biophysical properties similar to those of ATII cells.