Yield and functional properties of air-classified protein and starch fractions from eight legume flours.
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Fabaceae↗
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Determination of the molecular weight of proteins in heterogeneous mixtures: use of an air-driven ultracentrifuge for the analysis of protein--protein interactions.
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Molecular Weight↗
Effect of hypersensitivity on protein uptake across the air-blood barrier of isolated rabbit lungs.
In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood. In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance.
Absorption↗
Oxidative inactivation of the molybdenum-iron-protein component of nitrogenase from clostridium pasteurianum.
The sensitivity of the molybdenum-iron(MoFe)-protein of Clostridium pasteurianum nitrogenase toward oxidation has been studied by determining the enzymatic activity of this component after incubating it anaerobically in ferricyanide solutions of various oxidizing strengths (as measured by their oxidation potentials). It was found that the MoFe-protein remains active at potentials up to +350 mV (vs. standard hydrogen electrode) but becomes readily inactivated at more oxidizing potentials, after a lag period, depending on the potential level and temperature. Oxidative inactivation by ferricyanide results in the release of most of the Mo, Fe and S atoms from the protein which causes the loss of the absorption bands in the visible region. The metals and sulfur could be re-incorporated by incubation in a mixture containing thiol, sulfide, molybdate, and ferric iron. The EPR spectrum of the oxidatively inactivated MoFe-protein showed that both the high- and low-field signals are readily affected. Re-incorporation of the metals and sulfur into the "bleached" protein produced an EPR spectrum similar to that of the air-inactivated protein. Incubation of the Mo-Fe-protein with mersalyl abolished its enzymic activity. The difference spectrum before and after mersalyl treatment resembles that of the soluble spinach ferredoxin.
Clostridium↗
Aire mediates tolerance to insulin through thymic trimming of high-affinity T cell clones.
Insulin is a central autoantigen in the pathogenesis of T1D, and thymic epithelial cell expression of insulin under the control of the Autoimmune Regulator (Aire) is thought to be a key component of maintaining tolerance to insulin. In spite of this general working model, direct detection of this thymic selection on insulin-specific T cells has been somewhat elusive. Here, we used a combination of highly sensitive T cell receptor transgenic models for detecting thymic selection and sorting and sequencing of Insulin-specific CD4+ T cells from Aire-deficient mice as a strategy to further define their selection. This analysis revealed a number of unique t cell receptor (TCR) clones in Aire-deficient hosts with high affinity for insulin/major histocompatibility complex (MHC) ligands. We then modeled the thymic selection of one of these clones in Aire-deficient versus wild-type hosts and found that this model clone could escape thymic negative selection in the absence of thymic Aire. Together, these results suggest that thymic expression of insulin plays a key role in trimming and removing high-affinity insulin-specific T cells from the repertoire to help promote tolerance.
Animals↗
Retinopathy caused by a primary immune regulatory disorder - the spectrum of AIRE-associated retinopathy: case series and literature review.
BACKGROUND/OBJECTIVE: Retinal involvement in autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic autoimmune disorder caused by mutations in the AIRE gene, is increasingly recognised but remains poorly defined. Prior reports suggest a variable phenotype, ranging from mild changes to severe vision loss, often presumed untreatable. We explored the range of retinal phenotypes associated with AIRE gene deficiency in a multicentre case series of patients with APS1. METHODS: We performed a retrospective case note review of patients with molecularly confirmed APS1 from tertiary ophthalmic centres. Clinical history, multimodal retinal imaging, electrophysiology, genetic data, and treatment regimens were analysed. Histopathology was available in one case postmortem. RESULTS: Records were reviewed from five unrelated female patients. Median age was 14 years at onset of ocular involvement and 33 years at most recent follow up. Some findings from two cases have been previously reported. Three distinct pathogenic AIRE variants contributing to biallelic genotypes were observed. Retinal findings ranged from structurally and functionally normal to advanced degeneration. One patient demonstrated sharp zonal atrophy on histopathology. Inflammatory features predominated in two cases, both showing durable vision preservation with periocular or systemic immunomodulation. One patient demonstrated four years of disease stabilisation with rituximab. No consistent genotype-phenotype correlation emerged. CONCLUSION: AIRE-associated retinopathy encompasses a diverse spectrum, from clinically silent to profound degeneration. Early, targeted immunomodulation might preserve vision in selected cases. These findings advocate for ophthalmic surveillance in APS1, and support further investigation into predictive biomarkers and possible tailored immunotherapy in this vision-threatening autoimmune disorder.
Humans↗
Morphology of the hemostatic plug in human skin wounds: transformation of the plug.
The transformation of hemostatic plugs in human skin wounds was studied in vivo after bleeding had stopped. Standardized bleeding time incisions were made on the dorsal side of the forearm of four normal male volunteers. The wounds were excised by punch biopsy 10 minutes, 30 minutes, or 2 hours after they had been made and studied by light and electron microscopy. The wounds were filled with red blood cells, and a network of fibrin strands was found in the wound, particularly near transected vessels. Polymorphonuclear leukocytes were encountered within transected vessels and at 2 hours also in the wounds and in concentric rings around the vessels up to 0.5 mm. from the wound. On top of the wounds a superficial scab, consisting of red blood cells and presumably air-dried proteins, had formed. Hemostatic plugs were found at the ends of transected blood vessels. At 10 minutes the plugs consisted of largely degranulated platelets which showed strong interdigitation. Fibrin was still absent from the center of the plugs. At 30 minutes the platelets became less densely packed, and small fibrin fibers were deposited between the platelets in large peripheral areas of the plugs. At 2 hours some of the platelets had assumed rounded shapes with few interdigitations and larger spaces between them. Areas in the plug with platelets that had lost their integrity alternated with areas where platelets still had their cytoplasmic matrix and were interdigitated. Fibrin fibers were especially demonstrable between the degenerated platelet vesicles. This occurred everywhere in small hemostatic plugs and in the periphery of larger plugs. In one individual it was also observed in the center of large hemostatic plugs. In the other individuals fibrin was present centrally as amorphous dark staining material which was fibrillar in tangential sections.
Adult↗
Differential gene transcription following intravenous injection of air bubbles in rats with varying resistance to decompression sickness.
Decompression sickness (DCS) is a pathology caused by the appearance of gas emboli in the bloodstream and tissues. However, the weak correlation between the amount of venous gas emboli (VGE) and the development of DCS, as well as the considerable interindividual variability in DCS susceptibility, suggests that a higher DCS resistance could be associated with a better management of VGE-induced stress. To study the effects of VGE independently of the hyperbaric stress induced by diving, Wistar and DCS-resistant male and female rats received 5 mL/kg of a 0.9% NaCl solution containing air microbubbles through the tail vein. After 120 min, the liver and lungs were harvested. Wet-to-dry weight ratio was determined in the lungs. Gene expression was quantified by reverse transcription-polymerase chain reaction in the liver. Compared with standard Wistar, DCS-resistant rats exhibited a lower lung wet-to-dry weight ratio after air microbubble injection, suggesting lower pulmonary fluid accumulation. In the liver, DCS-resistant rats showed higher tissue factor transcription at the basal state and post-air microbubble injection. Tissue factor pathway inhibitor was lower in DCS-resistant rats at the basal state but higher following air microbubble injection. Levels of heat shock protein 70 (HSP70), heat shock protein 27 (HSP27), and early growth response 1 (Egr-1) were higher in DCS-resistant rats after air microbubble injection. At the basal state, only HSP27 was higher in DCS-resistant rats, with HSP70 lower and Egr-1 not different. These results help clarify the pathways involved in the response to VGE and highlight potential mechanisms underlying resistance to DCS, including enhanced anticoagulant pathways and improved cellular stress responses.NEW & NOTEWORTHY This study suggests for the first time that DCS resistance may be associated with a better tolerance to VGE. This greater DCS resistance could be achieved through improved control of the procoagulant effects of bubbles via TFPI-dependent inhibitory mechanisms and an enhanced cellular stress response to VGE by HSP70, HSP27, and EGR-1. It also suggests that it may be possible to stratify the individual DCS risk based on the thromboinflammatory response to bubbles.
Animals↗
Determination of ionized calcium in serum that has been exposed to air.
We examined changes in ionized calcium concentration in serum after its exposure to air. Samples with total protein concentrations ranging from 50 to 90 g/liter were equilibrated with CO2 in nitrogen (5/95, by vol) or CO2 alone, to produce pH values of 7.0 to 8.0. Ionized calcium was then measured with an Orion flow-through electrode system. Curves relating pH and ionized calcium concentration had statistically identical slopes regardless of protein concentration. A factor was derived, based on pH change, for correcting values for ionized calcium in serum exposed to air, and its validity was confirmed by comparing corrected values for samples allowed to stand at ambient temperature (23 degrees C) without anaerobic precautions with values initially obtained on anaerobic aliquots of the same samples.
Air↗
Strain-specific variation in the protein and lipopolysaccharide composition of the group B meningococcal outer membrane.
Variation in the protein and lipopolysaccharide composition of the meningococcal outer membrane may be due to either serotype differences or to changes in cultural conditions. There are 12 antigenically distinct serotypes of group B meningococci, and these are associated with distinct major outer membrane protein patterns on sodium dodecyl sulfate-polyacrylamide gels. In most strains the predominant outer membrane protein carries the serotype-specific determinant. Certain strains, when grown under similar conditions in different media showed an altered membrane composition. The type 2 strain, M986, grown in modified Frantz medium-A, had a reduced amount of the major 41,000-dalton protein while a 28,000-dalton protein predominated. The altered protein composition may be related to changes in cell metabolism as reflected by the pH of the medium after growth. Growth of the organism in Frantz medium-B caused a negligible drop in pH and the 41,000-dalton protein remained predominant. There was also variation associated with changes in the growth rate. Increasing the aeration caused a concomitant increase in growth rate and cell yield. We observed two quantitative changes in outer membrane proteins in four of seven strains examined: (i) where only a single major protein changed (three strains), and (ii) where an increase in one protein component was associated with a decrease in another protein (one strain). When the strains were grown in tryptic soy broth (Difco Laboratories, Detroit, Mich.) with either high or low aeration, the total protein in the outer membrane remained constant. In contrast, with high aeration there was a significant increase in lipopolysaccharide. These studies suggest that the cell surface proteins may be altered by the organism to meet a variety of environmental conditions.
Air↗
Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.
Human umbilical arteries are unique vessels in that they close quickly and completely at birth. It has been suggested that cyclic uanosine 3',5'-monophosphate (cAMP) in relaxation. This hypothesis has been evaluated in term gestational human umbilical artery segments incubated at 37 degrees C and in room air. (a) The basal cGMP content (1 pmol/mg protein) of artery segments incubated in room air was almost twice that of cAMP. (b) Bradykinin, histamine, serotonin, acetylcholine, and K+ ion, which cause umbilical artery constriction, can increase the cGMP content of the artery segments within 30 s of exposure without altering the cAMP content. (c) Prostaglandin E1, but not isoproterenol, caused accumulation of cAMP which is consistent with reports that umbilical arteries lack functional beta-receptors and that only prostaglandin E1 can bring about relaxation of umbilical arteries. (d) 1 muM atropine blocked the effect of 100 muM acetylcholine on cGMP content without altering the responses to histamine, bradykinin, serotonin, or K+ ion. (e) Pyrilamine (an H1 antagonist), but not metiamide (an H2 antagonist), blocked the effect of histamine on cGMP from which it is inferred that histamine causes accumulation of cGMP in umbilical artery via its interaction with H1 receptors. The results are consistent with the view that metabolism of the two cyclic nucleotides is independently controlled in the human umbilical artery and that cGMP is involved in contraction of the artery at birth.
Acetylcholine↗
Certain biochemical changes in the trachea, lungs, and heart of squirrels exposed to three principal air pollutants.
The fate of total lipids, proteins and carbohydrates in the trachea, lungs, and heart of the common ground squirrel, Funambulus pennanti, have been determined after separate exposure to three principal air pollutants, carbon monoxide (CO), sulphur dioxide (SO2), and nitrogen dioxide (NO2). Exposure to all of these gases produced edematous conditions; however, the moisture content of heart muscle was reduced. Carbon monoxide (CO) and NO2 are more toxic to pulmonary lipids than SO2. The lipid of the heart decreased, least effects noted with SO2 treatment. Mechanical properties of the lungs were changed by alteration of the lung lipids causing changes in the surface tension. Changes in protein content were caused by altered membrane permeability. Comparative data on the carbohydrates indicated adverse effects by the pollutants.
Air Pollutants↗
Mechanisms of inactivation of bacteriophage phiX174 and its DNA in aerosols by ozone and ozonized cyclohexene.
The mechanisms of inactivation of aerosolized bacteriophage phiX174 in atmospheres containing ozone, cyclohexene, or ozonized cyclohexene were studied by using 32P-labelled phage. The inactivation of the aerosolized phage in clear air or in air containing cyclohexene is due to damage of the protein coat since the deoxyribonucleic acid (DNA) extracted from the inactivated phage retains its biological activity. Inactivation of the phage in air containing ozonized cyclohexene is due both to protein and DNA damage. Sucrose gradient analysis shows that aerosolized inactivated phiX174 releases unbroken DNA. In contrast, the DNA from phage phiX174 inactivated by ozonized cyclohexene is broken. The inactivation of aerosolized phage phiX174-DNA was studied in the same atmospheres using 32P-labelled DNA. phiX174-DNA aerosolized in clear air or air containing cyclohexene at 75% r.h. is inactivated by a factor of 2 in 30 min. The inactivated DNA is broken. Ozone as well as ozonized cyclohexene inactivates KNA very fast causing breaks in the molecule. This is in contrast with the intact bacteriophage in which ozone does not produce breaks in the DNA.
Aerosols↗
Adsorption of plasma proteins on hydrophobic surfaces. I. Albumin and gamma-globulin.
The adsorption of albumin and gamma-globulin from solution at the liquid/air and liquid/liquid interfaces has been studied by the pendant drop technique as a model for the solid-liquid system. It is concluded that each protein adsorbs in a constant manner at the air, isooctane, and methylene iodide interfaces at equilibrium (1 hr), and the surface tension components of the protein layer presented to the hydrophobic phase have been found. The range of hydrophobic surfaces for which such constant behavior might be expected has been deduced, and it is shown that most common polymers lie within this range. A new model for protein adsorption is proposed, and the implications for biomaterials are discussed.
Adsorption↗
Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus.
The contribution of thymic antigen-presenting-cell (APC) subsets in selecting a self-tolerant T cell population remains unclear. We show that bone marrow (BM) APCs and medullary thymic epithelial cells (mTECs) played nonoverlapping roles in shaping the T cell receptor (TCR) repertoire by deletion and regulatory T (Treg) cell selection of distinct TCRs. Aire, which induces tissue-specific antigen expression in mTECs, affected the TCR repertoire in a manner distinct from mTEC presentation. Approximately half of Aire-dependent deletion or Treg cell selection utilized a pathway dependent on antigen presentation by BM APCs. Batf3-dependent CD8α⁺ dendritic cells (DCs) were the crucial BM APCs for Treg cell selection via this pathway, showing enhanced ability to present antigens from stromal cells. These results demonstrate the division of function between thymic APCs in shaping the self-tolerant TCR repertoire and reveal an unappreciated cooperation between mTECs and CD8α⁺ DCs for presentation of Aire-induced self-antigens to developing thymocytes.
Animals↗
Biological significance of piezoelectricity in relation to acupuncture, Hatha Yoga, osteopathic medicine and action of air ions.
Piezoelectric properties of biological macromolecules such as proteins, nucleic acids and mucopolysaccharides are reviewed in this paper. It is indicated that the structural elements of the human body composed of these piezoelectric substances are capable of transducing a mechanical energy into an electric current. Such a transduction may be brought about by movements of an acupuncture needle, osteopathic manipulations; Hatha Yoga postures or action of negatively charged air irons. It is postulated that electric current induced by stimulation of the specific sites on the surface of human body flows towards the internal organs along the semiconductive channels of biologic macromolecules. Electric current induced either by the piezoelectric transduction or directly applied from an external source may in turn stimulate individual cells in the target organ. Involvement of electrical phenomena in regulatory mechanisms on cellular and molecular levels is discussed.
Acupuncture Therapy↗
Interactions of band 3-protein from human erythrocyte membranes with cholesterol and cholesterol analogues.
The interaction between cholesterol and band 3-protein from human erythrocyte membranes was studied by incorporating the solubilized protein into monolayers of cholesterol and related sterols at the air-water interface and measuring the changes in surface pressure which accompanied protein incorporation. The following results were obtained: 1) Band 3-protein shows a very strong interaction with cholesterol monolayers. Both apolar and polar bonds contribute to this interaction. 2) Steroids with a structure slightly different from that of cholesterol (especially with respect to the polar group and the side chain) in most cases show a reduced affinity for band 3-protein. Thus, the protein-sterol interaction is highly specific. It is assumed that the protein-cholesterol interaction can be subidivided into two parts: an unspecific one which results from contributions from several sterol molecules, and a specific one which is due to the high affinity binding of the protein and cholesterol. The structural element responsible for the high affinity interaction is assumed to be a sterol-binding niche on the surface of band 3-protein. The sterol is thought to be held in the niche by a hydrogen bond at its polar head and a variety of hydrophobic bonds along its ring system and side chain.
Cholesterol↗
The biosynthesis of nitrogenase MoFe protein polypeptides in free-living cultures of Rhizobium japonicum.
The biosynthesis of the constituent polypeptides of nitrogenase component I (Rj 1) in free-living cultures of Rhizobium japonicum (strain 110) was investigated under different growth conditions. Cells were pulse-labelled and the proteins analysed by one and two-dimensional gel electrophoresis. The positions of the constituent Rj 1 polypeptides were identified by co-electrophoresis with purified Rj 1 isolated from bacteroids of soybean nodules, and by comparison with an immunoprecipitate from a culture induced for nitrogenase. The synthesis of the proteins preceded any detectable enzyme activity and increased with time, reaching a maximum after 3 days. At this time, between 6 and 8% of the total sodium dodecyl sulfate-soluble protein synthesized was Rj 1. Exposure to air led to a dramatic decrease in the rate of Rj 1 synthesis, with almost complete regression after 20 min. In the presence of KNO3, there was no nitrogenase activity, but the proteins were present in similar amounts (7%) as the control culture. When mannitol and glycerol were used as the sole carbon sources, the amount of Rj 1 synthesized was extremely low.
Gluconates↗