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Biomedical subjects

G Valle

Publications and source records attributed to G Valle.

At least 91 records · Page 5Linked to original sources
PubMed1989

Crystal-state structural analysis of two gamma-lactam-restricted analogs of Pro-Leu-Gly-NH2.

The crystal structures of two analogs of Pro-Leu-Gly-NH2 (1), containing a gamma-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastereomer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual "C5" conformation [psi 1 = -0.8(15) degrees] stabilized by a (peptide)N-H...N(amino) intramolecular H-bond [the N(3)...N(4) separation is 2.687(11)A]. Conversely, the N,N'-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a beta-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [phi 2 = 57.4(4), psi 2 = -129.9(3) degrees; psi 3 = -92.3(4), phi 3 = 6.4(5) degrees] lie close to the values expected for the corner residues of an ideal type-II' beta-bend. A weak intramolecular 4----1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C = O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the psi 1 torsion angle is 12.9(4) degrees and the intramolecular N(3)...N(4) separation is 2.321(4)A.

Lactams↗
PubMed1989

Crystallographic characterization of conformation of 1-aminocyclopropane-1-carboxylic acid residue (Ac3c) in simple derivatives and peptides.

The molecular and crystal structures of the C alpha,alpha-dialkylated alpha-amino acid residue 1-aminocyclopropane-1-carboxylic acid hemihydrate (H2+-Ac3c-O-.1/2 H2O) and nine derivatives and dipeptides have been determined by X-ray diffraction. The derivatives are pBrBz-Ac3c-OH, Piv-Ac3c-OH, Z-Ac3c-OH, the alpha-and beta-forms of t-Boc-Ac3c-OH, Z-Ac3c-OMe, and the 5(4H)-oxazolone from pBrBz-Ac3c-OH; the dipeptides are H-(Ac3c)-OMe and c(Ac3c)2. The values determined for the torsion angles about the N-C alpha (phi) and C alpha-C' (psi) bonds for the single Ac3c residue of Piv-Ac3c-OH, the alpha- and beta-forms of t-Boc-Ac3-OH and Z-Ac3c-OMe, and the C-terminal Ac3c residue of H-(Ac3c)2-OMe correspond to folded conformations in the "bridge" region of the Ramachandran map. The structures of pBrBz-Ac3c-OH and Z-Ac3c-OH, however, are unusual in having a semi-extended conformation for the phi, psi angles. The N-terminal Ac3c residue of H-(Ac3c)2-OMe adopts a novel type of C5 conformation, characterized inter alia by an (amino) N. . .H-N (peptide) intramolecular hydrogen bond. While the acyl N alpha-blocking groups form trans amides (pBrBz-Ac3c-OH and Piv-Ac3c-OH), the urethane groups may adopt either the trans [Z-Ac3c-OH and t-Boc-Ac3c-OH (alpha-form)] or the cis amide conformations [t-Boc-Ac3c-OH(beta-form) and Z-Ac3c-OMe]. The five- and six-membered rings of the 5(4H)-oxazolone and the 2,5-dioxopiperazine, respectively, are planar. The four independent molecules in the asymmetric unit of the free alpha-amino acid are zwitterionic.

Amino Acids↗
PubMed1988

Effect of anti-ER antibodies within the ER lumen of living cells.

We describe the production and partial characterization of 12 monoclonal antibodies raised against a preparation of endoplasmic reticulum membranes obtained from Xenopus laevis liver. Four of the antibodies cross-react with liver melanocytes; two of the antibodies recognize extracellular antigens, whilst the remaining six recognize antigens present in hepatocytes. The concentrations of these latter antigens increase markedly in livers stimulated by estrogen. Western blotting analysis revealed that the six anti-hepatocyte monoclonal antibodies recognize at least five different antigens whose molecular weights are 14K, 18K, 19K, 43K, and 125K. The possible functional involvement of the various antigens in the secretory pathway was investigated using Xenopus oocytes as a surrogate secretory system. The mRNAs coding for the monoclonal antibodies were injected into oocytes and the resulting immunoglobulin chains were translated and assembled into active anti-ER antibodies inside the lumen of the ER. The effect on secretion was then observed. Our data indicate that the binding of antibodies to most antigens of the endoplasmic reticulum membrane may result in a blockage of secretion.

Animals↗
PubMed1988

Enantioselectivity of muscarinic antagonists. Isomeric 2-cyclohexyl-2-phenyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodides.

The four isomers of 2-cyclohexyl-2-phenyl-5-[(dimethylamino)methyl] -1,3-oxathiolane methiodide were prepared. Their absolute configuration was attributed by means of X-ray crystallography and circular dichroism. The compounds were tested on rat bladder and guinea pig ileum and heart, and their antimuscarinic potency was evaluated and expressed as pA2. The results show that the introduction of a chiral center into position 2 brings about a small but definite enantioselectivity on rat bladder and guinea pig ileum which is not seen for guinea pig heart. This supports the view that differences exist among the muscarinic receptors of these tissues (M2 receptors). Comparison of the absolute configuration of the antagonists studied in this and in the preceding paper2 and that of strictly related agonists supports the hypothesis of a common binding site for agonists and antagonists of this kind.

Animals↗
PubMed1988

A statistical study on left ventricular peak filling rate in diabetes.

The importance of non-invasive evaluation of cardiac function in diabetes is well known and radionuclide angiocardiography has become an accepted diagnostic procedure. While the pathophysiological interpretation of systolic parameters is clear, the meaning and determinants of peak filling rate (PFR) remain rather speculative. In the present study, a "pattern recognition" approach, including principal component analysis and hierarchical cluster analysis, has been adopted in order to evaluate the determinants of PFR in a series of 48 non-selected diabetic patients. The results of the study show that: PFR is inversely dependent on age which is its main determinant when systolic function is preserved; PFR is inversely dependent on combined effects of left ventricular dimensions, angina and wall motion; and the duration of diabetes in itself does not influence PFR. These results lead to the following clinically relevant conclusions: (a) It is unlikely that a young diabetic patient without anginal symptoms will have a significant PFR impairment even if the diabetes has been present for a long time. If such impairment is however present, ventricular latent dysfunction is likely to be the cause even if systolic parameters are still normal; (b) A decrease of PFR in a middle-aged diabetic patient without symptoms and with normal systolic function cannot be equated with latent ventricular dysfunction as it may represent only an age-related physiological change without special diagnostic meaning.

Adolescent↗
PubMed1987

Conformational preferences and self-association modes of two diastereomeric statine derivatives.

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, 1H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.

Amino Acids↗
PubMed1986

Correlation of functional parameters derived by equilibrium radionuclide angiocardiography and left ventricular size in patients with old myocardial infarction.

A total of 131 patients with old (over 6 months) myocardial infarction (MI) and 18 normal subjects underwent equilibrium radionuclide angiocardiography at rest (rERNA). The following rERNA parameters were assessed: left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR), regional wall motion and a left ventricular size index. The patients with old MI were divided into four groups (I to IV) according to increasing left ventricular (LV) size, and the behaviour of the numerical parameters (LVEF, PER, PFR) was evaluated in each group. LVEF proved to be the most sensitive numerical parameter of overall LV performance. PFR decreased significantly from group I to group III but not from group III to group IV, suggesting that for extreme degrees of left ventricular enlargement some compensatory mechanism acts to prevent a too large fall in LV compliance. The effects of the site of the previous MI on LV performance were also evaluated. Both LV size and performance were least affected by postero-inferior MI. The LVEF was, however, a better predictor of LV size than the site of the MI.

Adult↗
PubMed1986

Right ventricular wall motion and performance in stabilized chronic respiratory failure evaluated by equilibrium radionuclide angiocardiography.

Equilibrium radionuclide angiocardiography (ERNA) was performed at rest in 30 patients with chronic respiratory failure (CRF) in order to evaluate right ventricular performance and wall motion. The usual indices of left ventricular performance were also recorded and correlated with right ventricular parameters. Only CRF patients without clinical, electrocardiographic or echocardiographic criteria suggestive of congenital, valvular, hypertensive or ischemic heart disease were studied. A RV dyskinesis was detected in 5 of the 30 patients, occurring however only in stage II-III CRF, as if a longstanding RV pressure overload were necessary for a RV dyskinesis to develop. No significant differences were found between patients with and without RV dyskinesis for all the functional ERNA parameters (i.e. LVEF, RVEF, PER, PFR). On the other hand, a significant correlation between the stage of the CRF and RVEF was observed.

Cardiac Output↗
PubMed1986

The effects of chronic hypoxia on left ventricular peak filling rate evaluated by equilibrium radionuclide angiocardiography.

Left ventricular peak filling rate (PFR) was measured by equilibrium radionuclide angiocardiography (ERNA) in 15 patients with Stage II stabilized chronic respiratory failure (CRF) without evidence of coexisting heart diseases and in 18 patients with coronary artery disease (CAD) without myocardial infarction. The study was designed to assess the effects of severe hypoxia and of ischaemia on the calcium-dependent early diastolic filling. PFR was found to be impaired in both groups of patients (mean = 1.72 EDVs-1 and S.E.M. = 0.07 in CAD; mean = 2.35 EDVs-1 and S.E.M. = 0.14 in CRF) but significantly less (p less than 0.001) in CRF patients while the left ventricular ejection fraction (LVEF) values were not significantly different between the two groups (mean = 60.0% and S.E.M. = 1.4 in CAD; mean = 62.0% and S.E.M. = 1.6 in CRF). As PFR is known to be a sensitive index of left ventricular performance the results obtained in this human model are consistent with findings obtained in animal models suggesting that hypoxia is less efficient than ischaemia in depressing left ventricular function.

Adult↗
PubMed1985

99mTc-DTPA clearance in bullous emphysema.

The degree of permeability of the alveolar-capillary barrier to low molecular weight solutes has been supposed to depend upon the radius of the epithelial pores. The bullous emphysema is a natural model in which this radius may increase because of the high tension in the bulla. Accordingly, the 99mTc-DTPA clearance may be expected to be faster than normal in lung fields including bullae. Results of the present study in which 99mTc-DTPA clearance was measured in six patients with bullous emphysema, seem to confirm this hypothesis at least to some extent. In fact, either increased or normal 99mTc-DTPA clearances were found over the lung fields including bullae communicating with the bronchial tree. Differences in both the size and the inner tension of the bullae as well as in the anatomical and functional conditions of the surrounding parenchyma are likely to account for such varying behaviour.

Capillary Permeability↗
PubMed1985

Left ventricular diastolic performance at rest in patients with angina and normal systolic function--assessment by equilibrium radionuclide angiography.

The aim of the study was to correlate diastolic function, as evaluated by peak filling rate (PFR) and relative time (TPFR), with the severity of ischemic heart disease, as evaluated by exercise electrocardiography. Accordingly, 83 ischemic patients with effort angina, but normal ejection function at rest and normal left ventricular size, were studied by equilibrium radionuclide angiocardiography within two weeks from the exercise ECG. Diastolic dysfunction, as determined from PFR and, to a lesser extent, from TPFR, is common in patients with ischemic heart disease and normal systolic function. The prevalence and severity of such dysfunction is related more to the severity of the ischemia, as evaluated by the exercise ECG, than to the presence of an old myocardial infarction. Such findings are consistent with the hypothesis that PFR reflects mainly the early diastolic active uncoupling process.

Adult↗
PubMed1984

Crystal structure of cyclo-L-histidyl-L-methionine and studies of metal complexation with divalent metal ions.

The structure of the title compound displays a buckled diketopiperazine ring. The two side-chains are both folded, with the imidazole ring facing the methionine chain. Imidazole nitrogen is the primary site for metal coordination of the ligand. Only for copper (II) adducts and in the solid state are there evidences of additional coordination through the sulfur atom.

Cations, Divalent↗
PubMed1983

Post-translational fate of variant MOPC 315 lambda chains in Xenopus oocytes and mouse myeloma cells.

The post-translational fates of three immunoglobulin lambda chain variants of MOPC 315 were investigated in mouse plasmacytoma cell lines and in mRNA-microinjected Xenopus oocytes. Quite unexpectedly we found that one non-secretory variant chain (lambda-43) underwent extensive post-translational N-glycosylation: however the presence of the oligosaccharide moiety did not account for the nonsecretory phenotype nor did it affect the rate of degradation of this lambda chain. Another variant chain (lambda-47) at first believed to be non-secretory, was found to be secreted from oocytes at a very low level, but mostly as a lambda-lambda dimer. In myeloma cells a low level of lambda-47 chain was secreted and again lambda-lambda dimers were the favoured secretory form. The secretory lambda-48 chain also formed lambda-lambda dimers, whereas lambda-43, which was never secreted, was only found as a monomeric lambda chain in both oocytes and myeloma cells. A similar relationship between assembly and secretion was found when oocytes were coinjected with MOPC 21 heavy (gamma 1) chain mRNA and MOPC 315 lambda chain mRNAs. The wild type lambda chain (lambda-48) was able to assemble with the gamma chain in a covalently bound tetramer (gamma gamma lambda lambda). The variant lambda-47 chain was also able to form gamma gamma lambda lambda tetramers, whereas the lambda-43 was not, even when glycosylation was prevented by tunicamycin. Both types of tetramer were secreted. These data reinforce the idea that conformational changes play a major role in the routing of secretory proteins and that the cellular mechanisms by which these changes are recognized are not cell-type specific.

Animals↗
PubMed1983

The oocyte as a secretory cell.

Xenopus laevis oocytes secrete a large variety of foreign secretory proteins after the microinjection of mRNA or DNA. Two classes of such proteins are discussed in detail. These are the chick oviduct proteins ovalbumin and lysozyme, and the mouse MOPC 21 immunoglobulin. The injection of mRNAs for mouse immunoglobulin heavy or light chain leads to the synthesis, segregation, but not secretion of the encoded proteins unless the two mRNAs are simultaneously or sequentially injected into the same oocytes. Chicken ovalbumin and lysozyme are synthesized and secreted from oocyte after the injection of either oviduct mRNA or cloned DNA (ovalbumin). The secreted lysozyme is exported considerably faster than ovalbumin; however, 40% of the lysozyme synthesized cannot be secreted and, after fractionation of oocytes on sucrose gradients, is found in a higher density position than ovalbumin. No competition at the level of secretion or translation was noted when different amounts of immunoglobulin and ovalbumin mRNAs were injected into oocytes. However, the co-injection of ovalbumin mRNA and mRNAs encoding anti-ovalbumin immunoglobins resulted in the formation of a complex of the two types of protein within the oocyte. In these circumstances, secretion of the immunoglobulin was severely reduced.

Animals↗
PubMed1983

Echotomography in arteriovenous fistulae.

We employed Echotomography (by 2.25-5MHz probes) as a quick procedure to measure the vessel diameter at definite points to detect aneurysms and their evolution, to evaluate the arteriovenous fistula (AVF) characteristics, to detect haematoma, thrombi, and collateral vessels. Echotomography is a non-invasive technique which may be performed repetitively even immediately after AVF surgery. It was most valuable in the examination of proximal AVF and internal shunts (autologous venous and bovine carotid grafts). Echotomography has proved to be accurate in studying the initial morphological and functional evaluation and follow-up of AVF.

Arteriovenous Shunt, Surgical↗