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J Edelman

Publications and source records attributed to J Edelman.

14 recordsLinked to original sources
PubMed1992

Pair distribution functions in small systems: implications for protein structure analysis.

A general formula is derived for the relation between the pair correlation function and the histogram of interparticle distances in small nonuniform systems. The formula is applied to random packings of spheres in a spherical container, which are generated by a Monte Carlo method. When measured properly, the resultant correlation functions are very similar to ones in bulk systems with the same volume fraction of particles. In contrast, the density is very nonuniform as a function of distance from the center of the container. The variation is an order of magnitude for the number density of particle centers, or severalfold for the occupied volume fraction. It is described how these results can be used to analyze the forces that determine protein structure.

Amino Acids↗
PubMed1992

The low-temperature heat capacity of solid proteins.

Several harmonic models of protein fluctuations are used to calculate the heat capacity. They get the spectral density of conformational modes from inelastic neutron scattering, normal mode calculations, or macroscopic elasticity (Debye model). It is assumed that the low-frequency spectral density depends only weakly on temperature and protein species. The Debye model predicts temperatures below which modes are primarily in their ground states: 10 and 80 K for the lattice and conformational modes, respectively. The models differ most below 100 K. The mode calculations yield the most accurate predictions, though all three models are within twofold of the data. The heat capacity has the power law form aTb for T less than 30 K. The experimental b's of proteins are 1.6-1.8, and the theoretical, 1.1-1.3. One possible explanation for the discrepancy is the occurrence of transitions between discrete conformations. All of the models approach the measured data in the range 100-200 K. They are very similar above 200 K, where the heat capacity includes significant contributions from bond stretching and bending. This masks the possible anharmonic behavior of the conformational modes. Hydration substantially increases the heat capacity above 200 K. This effect seems to be a consequence of conformational transitions that have higher energy than the ones seen with low hydration. The analysis also predicts that denaturation with constant hydration produces a negligible increase of heat capacity. The larger increment in solution arises from the different hydration of the folded and unfolded states, and is responsible for the existence of cold denaturation. This phenomenon is thus predicted not to occur when the hydration is constant.

Calorimetry↗
PubMed1992

Lipopolysaccharide-induced stimulation of alveolar macrophage opsonin-independent phagocytosis.

Alveolar macrophage (AM) opsonin-independent phagocytosis may be an important process by which bacteria are cleared from the airspaces. Although it has been shown that clearance of bacteria from the lung is altered in association with endotoxemia, the effect of endotoxemia on opsonin-independent phagocytosis is unknown. Because alterations in AM opsonin-independent phagocytosis could potentially influence bacterial clearance in the lung, we studied the effects of the intravenous injection of Escherichia coli lipopolysaccharide (LPS) into rats on AM opsonin-independent phagocytosis of latex particles. AM obtained by bronchoalveolar lavage (BAL) 2 or 4 hr after injection of LPS demonstrated phagocytosis comparable to AM from control animals. In contrast, AM obtained 12 hr after injection of LPS demonstrated a nearly threefold increase in phagocytosis. Depletion of serum complement with Naja naja cobra venom factor (CVF) did not alter LPS-induced augmentation of phagocytosis. Furthermore, phagocytosis of AM obtained by BAL 2 or 12 hr after activation of complement by injection of CVF was not significantly different from that of AM from control animals, indicating that complement activation alone was not sufficient to stimulate opsonin-independent phagocytosis. These observations suggest that opsonin-independent phagocytosis may represent an important route of bacterial uptake by AM following endotoxemia, and that LPS-induced stimulation of AM opsonin-independent phagocytosis may occur independently of activation of complement by LPS.

Animals↗
PubMed1992

Comparison of two yttrium-90 regimens in inflammatory and osteoarthropathies.

Two yttrium-90 (90Y) radiosynovectomy procedures were compared. One procedure, performed at the Royal Perth Rehabilitation Hospital (RPRH) required a shorter immobilisation time than that performed at the Sir Charles Gardiner Hospital (SCGH). There were no significant differences in outcome between the two procedures for the groups with inflammatory and osteoarthropathy. Thirty two patients (45 joints) with inflammatory arthropathy were treated (25 with rheumatoid arthritis, three with psoriatic arthritis, two with ankylosing spondylitis, and two with unspecified inflammatory arthropathy) and 40 patients (58 joints) with osteoarthropathy. A separate assessment of local lymph node spread in patients treated by the RPRH showed a minor spread of 90Y in one of 37 joints assessed. A marked improvement in the patient evaluation scores in the inflammatory arthropathy group at three months persisted at 12 months. Good lasting responses were more common in patients with inflammatory arthropathy with a normal joint or early radiological disease. A marked improvement in the pain and evaluation scores occurred at three months in the group with osteoarthropathy but had disappeared by six months after treatment.

Arthritis, Psoriatic↗
PubMed1991

Lipopolysaccharide-induced pulmonary vascular sequestration of polymorphonuclear leukocytes is complement independent.

Lipopolysaccharide (LPS) injected intravenously produces leukopenia and sequestration of polymorphonuclear leukocytes (PMN) in the pulmonary vascular bed. To evaluate the role of complement in this process, we used C5-sufficient (B10.D2/nSn) and C5-deficient (B10.D2/oSn) mice and Sprague-Dawley rats depleted of complement with Naja naja cobra venom factor (CVF). We found a comparable increase in the number of PMN in lung tissue of C5-sufficient and C5-deficient mice given Escherichia coli LPS (0127:B8, 3 mg/kg), revealing that LPS acts independently of C5 and its biologically active fragments. Intravenous injection of LPS (3 mg/kg) into rats caused significant intravascular complement activation as assessed by serum CH50 and resulted in an almost 10-fold increase in numbers of PMN in lung tissue. Pretreatment of rats with CVF (50 U) did not reduce LPS-induced PMN sequestration, suggesting that the process is independent of C3. As reported previously, we found large numbers of PMN in bronchoalveolar lavage samples of 24 h after injection of LPS (3 mg/kg). Complement depletion did not prevent LPS-induced migration of PMN. No PMN migration occurred 2, 6, 12, 24, or 48 h after injection of CVF alone, indicating that complement activation is not sufficient to cause PMN migration. In contrast to our findings in rats, no PMN migrated into airspaces of C5-sufficient and C5-deficient mice 24 or 48 h after injection of LPS (3 to 20 mg/kg).

Animals↗
PubMed1990

Immunohistochemical and molecular analysis of beta 1 and beta 3 integrins.

The expression and function of integrin subunits was examined by immunohistochemical staining of normal and malignant tissues and by producing specific changes in avian beta subunit cDNA that were subsequently expressed in mammalian cells. Most tissues express only a restricted number of integrins. These include primarily those thought to function as collagen/laminin receptors. With the exception of metastatic melanomas, tumors show a general down regulation of integrins. Structure/function studies of the beta subunit show that the cytoplasmic domain is required for inclusion in adhesion plaques and for promotion of adhesive functions; that the transmembrane domain is required for subunit association, but not proper alpha subunit selection; and that the amino terminal one third of the subunit must remain intact for subunit selection and ligand binding to occur.

Animals↗
PubMed1989

Linear optimization of predictors for secondary structure. Application to transbilayer segments of membrane proteins.

Sliding-window averaging of amino acid properties is a standard method for predicting protein secondary structure. For example, transmembrane segments are predicted to occur near the peaks in a hydropathy plot of a membrane protein. Such a scheme (linear convolutional recognizer, LCR) assigns a number (weight) to each type of monomer, and then convolutes some window function with the sequence of weights. The window has commonly been rectangular, and the weights derived from singlet amino acid frequencies in proteins of known secondary structure or from physical properties of amino acids. The accuracy of the windows and weights have remained unknown. We use linear optimization theory to develop a general method for approximating the optimal window and weights for a LCR. The method assumes that one knows the sequences of one or more chains and the locations of their "features", regions having the secondary structure of interest. We present formulae for quantifying the accuracy of predictors. We show why the optimal LCR is more accurate than methods based on the differences between singlet monomer frequencies inside and outside features. The advantage of an optimal LCR is that its weights inherently include correlations between nearby monomer positions. The optimal predictor is not perfect though. We argue that its inaccuracy is an intrinsic limitation of linear predictors based on monomer weights. As a practical example, we study predictors for transbilayer segments of membrane proteins. We estimate the optimal weights and windows for the two bacterial photosynthetic reaction centers whose three-dimensional structures are known. The resultant LCR, which is more accurate than previous ones, is still inexact. We apply it to bacteriorhodopsin and halorhodopsin. Several non-linear generalizations are examined as possible improvements to the LCR method: non-linear combinations of linear predictors and windowed Fourier transforms of the weight sequences. The former do not significantly increase the accuracy, while the latter reveal a weak negative correlation between the segments and periodic variations of the weights.

Amino Acids↗
PubMed1989

Lipopolysaccharide stimulates alveolar macrophage adherence in vivo and in vitro.

The number of alveolar macrophages (AM) obtained from rats by bronchoalveolar lavage (BAL) decreases significantly within two hours after infusion of E. coli lipopolysaccharide (LPS). To investigate the mechanism of this phenomenon, we evaluated adherence properties of AM obtained from rats 4 hours after intravenous injection of E. coli LPS (3 mg/kg) or normal saline (NS). Significantly fewer AM were present in BAL samples from LPS-treated rats (4.09 x 10(6] compared to NS-treated rats (7.55 x 10(6]. When a 17 mM lidocaine solution (LDC) was used for lavage, the number of AM in BAL samples from LPS-treated rats increased significantly (7.38 x 10(6]. Adherence of AM from LPS-treated rats to rotating plastic tubes was significantly greater than that of AM from NS-treated rats. Incubation of normal AM with LPS (5 or 15 micrograms/ml) in serum-free media increased AM adherence to plastic. LPS-induced adherence was significantly greater at the higher LPS dose. Thus, the decreased number of AM obtained by BAL of LPS-treated rats appears to be due to increased adherence of AM to alveolar structures. This phenomenon may be mediated by direct effects of LPS on AM.

Animals↗
PubMed1989

Cathepsin B and D activity in alveolar macrophages from rats with pulmonary granulomatous inflammation or acute lung injury.

Cathepsin B and D activity was determined using specific synthetic substrates in alveolar macrophages (AMs) obtained from Sprague-Dawley rats with experimentally induced pulmonary granulomatous inflammation. Increased cathepsin B activity was found 4 days after intravenous injection of complete Freund's adjuvant (CFA), but not after injection of live bacillus Calmette-Guérin organisms (BCG), indicating that the enzyme response was unrelated to the subsequent development of granulomatous inflammation. Findings of comparable increases in enzyme activity following injection of mineral oil (MO) indicate that the response to CFA was due to the oil component. Significantly, oleic acid (OA), a natural fatty acid, did not stimulate enzyme activity although the agent, like MO, caused acute lung injury as assessed by 125I albumin uptake. At 7 and 28 days following injection of CFA, cathepsin B levels in AMs were the same as those in animals given normal saline (NS), although bronchoalveolar lavage (BAL) samples still contained increased numbers of AMs, and cells obtained at 28 days phagocytosed more polystyrene microspheres. Cathepsin D activity did not increase 4 days after injection of CFA or BCG + CFA; at 28 days following injection of BCG + CFA activity was significantly decreased as compared to animals given NS. The data reveal a differential response of two lysosomal enzymes during the early phases of granulomatous inflammation.

Albumins↗
PubMed1988

Effect of intra-articular glucocorticoids on the disposition of sulphadimidine in chronic osteoarthritis patients.

1. The disposition of sulphadimidine (15 mg kg-1 orally) was investigated in six chronic osteoarthritis patients (four slow and two fast acetylators) prior to and 4 days following intra-articular administration of glucocorticoids. 2. The mean (+/- s.e. mean) renal clearance of sulphadimidine was increased from 0.03 +/- 0.01 to 0.07 +/- 0.02 ml min-1 kg-1 (P = 0.01) following the administration of intra-articular steroid. 3. Mean metabolic clearance and volume of distribution data were similar on the two study days. However, two of the slow acetylators showed marked increases (63% and 193%) in metabolic clearance following steroid treatment.

Acetylation↗
PubMed1985

Commodities into food.

It is not surprising that past predictions of the extent of adoption of new technology by the food and agricultural industries have only been partly realized. This is a result of the difficulty of forecasting the take-up of technology that is capable of being transferred from other industries, for example, process control methods and the advent of new packaging materials. Most technology that is adopted is normally incremental over the existing technology and forecasting of this type is best done by specific experts within the industry. Factors which influence uptake of technology in the food industry include not only the available technology, but also the supply of raw materials, economics and disposable income, food habits, health and nutrition and market requirements. In addition to these there is legislation, which imposes compositional, labelling and trade requirements on grower, processor and retailer. New products and processes are determined by all these factors, the overriding influence being the consumer's requirement for palatable and nutritious foods that provide value for money. In the cereals-processing industry significant developments have taken place in the provision of U.K. wheat varieties for breadmaking. The U.K. is now in the position where the bulk of its breadmaking wheats are homegrown. Further advances can be make by investing in applied research into those characteristics of bread wheats which are determinants of good bread flours, that in turn will help in the provision of suitable bread wheat varieties. A less traditional area is that of flour fractionation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗