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Biomedical subjects

A Pastore

Publications and source records attributed to A Pastore.

At least 145 records · Page 8Linked to original sources
PubMed1989

The dynamic properties of melittin in solution. Investigations by NMR and molecular dynamics.

Molecular dynamics simulations are described for the peptide melittin. The atomic trajectories are calculated both with normal potential energy functions and with additional distance restraints deduced from nuclear Overhauser effects observed in NMR experiments. The results are compared with NMR data on coupling constants and amide exchange rates and with B-factors from X-ray crystallography. The observed correlations between experiment and molecular dynamics simulations suggest a relatively mobile C-terminus and relatively high flexibility around residue 11. It is noted that the high conformational variation around residue 11 is due in part to the presence of a proline at position 14 which results in a "missing" H-bond in the largely alpha-helical structure. It is also noted that a proline is a common feature of many putative membrane spanning helices. A role for such prolines is suggested.

Bee Venoms↗
PubMed1989

Increased serum levels of IgA1-IgG immune complexes and anti-F(ab')2 antibodies in patients with primary IgA nephropathy.

A solid-phase ELISA was used to detect IgA1 immune complexes (IgA1 ICs) containing IgG and IgM in 38 serum samples from 30 patients with primary IgA nephropathy (IgAN) and 14 subjects with non-IgA chronic glomerulonephritis. A jackfruit lectin, jacalin, was used as the substrate for the selective binding of human IgA1 ICs in serum PEG precipitate (7%). The presence of IgG, A and M antibodies against the F(ab')2 region of IgG was also investigated by the solid-phase ELISA. Six patients were studied during remission and relapse (fever, upper respiratory tract infection and macroheamaturia). The results showed significant increases in serum levels of IgA1 ICs (P less than 0.001) in 39.4% of the IgAN patients, IgA1-IgG ICs (P less than 0.001) in 68.4%, and IgA1-IgM ICs (P less than 0.002) in 10.5% of the patients. A significant increase in IgA1-IgG ICs was observed during relapse (P less than 0.02). Significantly high values of IgG (P less than 0.003) and IgA (P less than 0.001) antibodies directed at the F(ab')2 region of IgG were found. A significant increase in anti F(ab')2 antibodies (class IgA and IgM) was seen in the acute phase of the disease. The data suggest that an increased production of IgA1 ICs occurs in IgAN patients; ICs are mainly IgA1-IgG ICs during relapse. The presence of high serum levels of IgG and IgA antibodies against the F(ab')2 region of IgG indicates that in addition to the multiple anomalies of IgA regulation described in IgAN patients there may be further aberrances.

Adolescent↗
PubMed1989

Influence of different dialyzer membranes on plasma fibronectin levels in hemodialyzed patients.

Plasma fibronectin (FN) was assayed in 30 patients with chronic renal failure under conservative therapy, 60 uremic patients undergoing periodic hemodialysis, and 7 patients treated by hemofiltration. Plasma FN was significantly lower in uremic patients on conservative therapy and in those who received intermittent hemodialysis than in the control group. No difference was seen between mean FN concentrations using different dialyzer membranes. Nevertheless, plasma FN levels were significantly higher in subjects after intermittent hemofiltration. There was no evidence of activation of the coagulation system or of any correlation between FN and fibrinogen values. These findings suggest that conventional hemodialysis is not effective in improving the low levels of plasma FN found in uremic patients, whereas intermittent hemofiltration raises FN. These differences may be due to the fact that during hemofiltration, even when using the same dialyzer membranes as in conventional hemodialysis, some "substances" with high molecular weight that could block the synthesis of FN could be removed.

Adult↗
PubMed1988

Polymeric IgA and IgA rheumatoid factor decrease the capacity of serum to solubilize circulating immune complexes in patients with primary IgA nephropathy.

Primary IgA nephropathy (IgAN) is characterized by the presence of immune complexes (IC), high levels of polymeric IgA (pIgA), and IgA rheumatoid factor (RF) in the blood. The impaired capacity of serum to solubilize IC in the presence of normal values of C hemolytic activity as well as high serum levels of C3, C4, and properdin factor B have led us to analyze whether pIgA and IgA RF from patients with IgAN where capable of inhibiting the capacity of normal human serum to solubilize immune precipitates (BSA-anti-BSA) preformed at equivalence. The results showed a significant reduced mean capacity of serum from patients with IgAN to solubilize "in vitro" immune precipitates (p less than 0.001) and significant high mean levels of pIgA (p less than 0.001) and IgA RF (p less than 0.005) in the blood. Increasing amounts of pIgA inhibited solubilization of IC in the fluid phase, and inhibitory activity was also shown by the IgA RF. There were inverse correlations between pIgA and the capacity of serum to solubilize IC (r = -0.36; p less than 0.05), and between IgA RF and the complement-mediated solubilization (r = -0.57; p less than 0.001). It is suggested that pIgA and IgA RF may be responsible for the impaired complement-mediated solubilization of serum and the persistence of insoluble nephritogenic IC in the blood of patients with primary IgAN.

Adolescent↗
PubMed1988

The structure of melittin. A 1H-NMR study in methanol.

The conformation of the 26-residue polypeptide melittin has been studied using 1H-NMR spectroscopy in methanolic solution. The 1H-NMR spectrum of melittin has been assigned using two-dimensional NMR techniques and the secondary structure has been calculated from nuclear Overhauser enhancement data using distance geometry and restrained molecular dynamics analyses. The structure is found to be mainly helical, and similar to that found in crystals from diffraction data: residues 2-11 and 13-26 form regular alpha-helices joined by a 'hinge' between residues 11-12. The structure in this hinge region is shown to be significantly different from that in the crystal structure, leading to a smaller angle between the two helices. The possible significance of the proline residues in this and similar membrane-spanning peptides is discussed.

Amino Acid Sequence↗
PubMed1988

High-resolution 1H NMR study of the solution structure of delta-hemolysin.

The 26-residue toxin from Staphylococcus aureus, delta-hemolysin, is thought to act by traversing the plasma membrane. The structure of this peptide, in methanol solution, has been investigated by using high-resolution NMR in combination with molecular dynamics calculations. The 1H NMR spectrum has been completely assigned, and it is shown that residues 2-20 form a relatively stable helix while the residues at the C-terminal end appear to be more flexible. The structures were calculated only from nuclear Overhauser effect data and standard bond lengths. It is shown that the results are consistent with 3JNH-alpha CH coupling constants and amide hydrogen exchange rates.

Bacterial Proteins↗
PubMed1988

Structural alignment and analysis of two distantly related proteins: Aplysia limacina myoglobin and sea lamprey globin.

Two new globin structures have recently been determined at high resolution: the globin from the mollusc Aplysia limacina at 1.6 A resolution and a new refinement of the structure from sea lamprey. Two amino acid sequences of these homologous molecules have only 30% residue identity in an optimal alignment. We discuss some of the problems arising in the alignment of Aplysia globin with other globins of known structure, a challenging problem because of the distant relationship. Four independent approaches were applied to the alignment of the Aplysia and lamprey globins, including those based on individual sequence comparisons, structural analysis, and the relatively new method of templates or fingerprints derived for an entire family of proteins. We also compare these two new structures with what is already known about the globin family. A detailed description of the two structures shows that the two molecules contain the main structural features common to all the globins so far studied, with several minor but interesting hitherto unobserved variations.

Amino Acid Sequence↗
PubMed1988

The role of polymeric IgA in complement-mediated solubilization of IgG and IgA immune complexes.

Sera from patients with IgA nephropathy (IgAN) have a reduced capacity to solubilize immune complexes. The in vitro complement-mediated solubilization of immune complexes containing IgG (bovine serum albumin [BSA]-anti-BSA) or IgA (DNP29-BSA-anti-DNP) was decreased, despite normal serum levels of complement. The close correlation between low values for complement-mediated solubilization and high serum levels of polymeric IgA and/or IgA rheumatoid factor indicates that these macromolecules interfere with the process. These findings suggest that polymeric IgA produced during stimulation of mucosae specifically interferes with immune complex solubilization. Further studies are necessary to elucidate the mechanisms. The decreased complement-mediated solubilization in patients with IgAN could be responsible for persistently high levels of immune complexes containing IgA or IgG in the circulation and their continual deposition in the mesangium.

Antigen-Antibody Complex↗
PubMed1987

Experimental attempt to simulate receptor site environment. A 500-MHz 1H nuclear magnetic resonance study of enkephalin amides.

The amides of Leu5-enkephalin, Met5-enkephalin, and three analogues, D-Ala2,Leu5-enkephalin, (AcO)Tyr1,Met5-enkephalin, and (AcO)Tyr1,D-Ala2,Met5-enkephalin, have been studied by means of 1H NMR spectroscopy in two different solvent systems: Me2SO-d6 and CDCl3. In the latter solvent the peptides were dissolved as complexes with 18-crown-6-ether, a coronand that binds strongly to the NH3+ groups. The crown ether complexation and the apolar solvent were used to simulate the anionic subsite of the receptor and the hydrophobic environment of the receptor cavity, respectively. The very unusual amide proton chemical shifts and their temperature coefficients suggest the presence of folded conformations in CDCl3 for all peptides, consistent with several models of opioid receptors and with the crystal structure of Leu5-enkephalin. The differences among the proposed cyclic conformations of the five peptides may be correlated, in part, with their different biological activity. All peptides in Me2SO-d6 are characterized by complex mixtures of extended fully solvated conformations.

Enkephalin, Leucine↗
PubMed1987

Structure and dynamics in oligomannose-type oligosaccharides.

Using a combination of 1H NMR nuclear Overhauser effect measurements, molecular orbital calculations, and molecular dynamics simulations, we have determined the tertiary structure and dynamic properties of the oligomannose oligosaccharide Man alpha 6(Man alpha 3)Man alpha 6(Man alpha 3)Man beta 4GlcNAc beta 4GLcNAc. While the calculated potential surfaces for the majority of the glycosidic linkages could be described by a single deep potential well, similar calculations for the Man alpha 1-6Man alpha and Man alpha 1-6Man beta linkages described a diffuse, shallow well, suggesting that a larger degree of flexibility exists about the latter. These conclusions are supported by the results of molecular dynamics simulations, which suggest that the NMR data should be interpreted in terms of a degree of flexibility about the Man alpha 1-6Man beta and Man alpha 1-6Man alpha linkages. In contrast, a similar series of investigations suggests that the conformation of the Man alpha 1-6Man beta linkage in Man alpha 2Man6(Man alpha 2Man alpha 3)Man alpha 6 (Man alpha 2Man alpha 2Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc is more restricted, resulting in an overall structure that is "restrained".

Carbohydrate Conformation↗
PubMed1987

A 500-MHz proton nuclear magnetic resonance study of mu opioid peptides in a simulated receptor environment.

The structure-activity relationship of several mu selective opioid peptides has been evaluated on the basis of both experimental and theoretical approaches. The conformations of Tyr-D-Ala-Phe-Gly-NH2, the tetrapeptide N-fragment of dermorphin, and two analogues have been studied in solution by 1H NMR spectroscopy. The physicochemical environment inside the receptor has been simulated by complexing the peptides with a crown ether and dissolving the complexes in chloroform. The family of conformations derived from the NMR data possesses most of the features previously proposed for mu agonists and is fully consistent with an original model of the mu receptor based on the structures of many rigid opiates. As a simple test of this model, the synthesis of a linear peptide with significant mu activity in spite of the absence of Tyr1 is reported.

Animals↗
PubMed1986

Increased immunoglobulin-secreting cells in the blood of patients with active idiopathic IgA nephropathy.

Peripheral blood lymphocytes from 33 patients with idiopathic IgA nephropathy (IgAN) and 15 healthy controls were stimulated in vitro by Protein A from Staphylococcus Cowan I; immunoglobulin (Ig) production was measured by a reverse hemolytic plaque assay to evaluate the quantity of cells secreting Ig. In addition, serum Ig levels, circulating IgG, IgA and IgM immune complexes (ICs) and the Fc and C3b receptor mediated phagocytosis of peripheral monocytes were measured. The laboratory findings in different phases of the disease were compared. The mean level of IgA-plaque forming cells (IgA PFC) in IgAN patients with normal renal function was significantly higher (p less than 0.001) than the mean control value. In contrast, they were reduced significantly in those patients who were subjected to periodic hemodialysis (p less than 0.001). Disease activity produced a significant increase in IgG PFC and IgA PFC, high IgG and IgM serum levels, high circulating IgG ICs, and low C3b-mediated phagocytic function of the peripheral macrophages. These findings demonstrate that IgAN is associated with an increased number of IgG and IgA-secreting cells in the peripheral blood of patients during the active phase of the disease and that the concurrent presence of high levels of circulating Ig ICs may be responsible for the gross hematuria, as their deposition in the glomeruli could activate the complement system.

Adolescent↗
PubMed1985

A conformational study of the opioid peptide dermorphin by one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy.

Dermorphin, a natural peptide opioid containing a D-Ala2 residue, has been studied in dimethyl sulfoxide (DMSO) solution by means of several one-dimensional and two-dimensional 1H nuclear magnetic resonance (NMR) methods at various fields from 80 to 600 MHz. The combined use of conventional NMR parameters and of nuclear Overhauser effect effects points to an essentially extended structure. This conformation may be, in part, the result of strong interaction of the amide groups with DMSO molecules.

Dimethyl Sulfoxide↗
PubMed1985

[Not Available].

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History, Modern 1601-↗
PubMed1985

Effects of plasma-exchange on complement-mediated solubilization of circulating immune complexes in patients with systemic lupus erythematosus.

In an uncontrolled clinical trial the effects of plasma-exchange (PE) on the capacity of the serum to solubilize circulating immune complexes were studied in patients with active systemic lupus erythematosus. Four patients were treated with immunosuppressive therapy alone, while others were also treated by PE over a period of four to seven weeks. Plasma was replaced by fresh frozen plasma in the final part of each procedure. All patients showed evidence of clinical improvement at the time of treatment. Furthermore, PE was demonstrated to reduce drastically the number of relapses. An improvement of the capacity of solubilize immune complexes in vitro associated with a persistent fall in the levels of the circulating immune complexes was observed in patients treated with PE. This suggests that fresh frozen plasma improves the clearance of immune complexes and reduces the frequency of relapses. In our experience, clinical improvement and/or resolution of the symptoms seems to be related to the decrease in serum immune complex levels, while clinical relapses seem to parallel the behaviour of complement-mediated solubilization.

Adolescent↗