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Biomedical subjects

A Motta

Publications and source records attributed to A Motta.

At least 109 records · Page 6Linked to original sources

[Impacted maxillary third molars. Accidental dislocation].

During surgical removal of impacted maxillary third molars, many complications may occur. Their accidental displacements in the maxillary sinus or in the infratemporal fossa are not too rare in the common general dentistry. Presenting this case, the Authors want to demonstrate that, when each one of this kind of teeth are well studied before their treatment, many complications can be avoided and, the sooner the dentist is able to solve them when they occur, the better the post-operative course will be.

Adult↗

Cyclic hexapeptides related to somatostatin. Conformational analysis employing 1H-NMR and molecular dynamics.

We report the conformational analysis of a series of cyclic hexapeptides related to the hormone somatostatin utilizing 1H NMR spectroscopy and NOE restrained molecular dynamics. The conformational preferences and results from biological analysis of these analogs (previous paper) allow for refinement of the current understanding of the structure-activity relationship of somatostatin. For most of the molecules examined, a beta II' turn about the D-tryptophan-lysine residues, postulated to be required for biological activity, was present. From the NOE restrained molecular dynamics, it can be seen that the turn structure is important for the maintenance of the proper orientation of the side chains of the adjacent phenylalanine, tryptophan and lysine. The biologically active analogs have the side chains of lysine and D-tryptophan extended away from the 18-membered ring in close proximity to each other for a significant portion of the dynamic simulations. Although other conformations are accessible and monitored during the simulations, we believe this is important for biological recognition. The absence of the beta II' turn at the D-tryptophan-lysine disrupts this side chain array producing inactive molecules. The role of the bridging region, the Phe-Pro dipeptide, is to stabilize the beta II' turn and help maintain the proper orientation of the biologically important side chains.

Amino Acid Sequence↗

Epidemiology of young strokes in rural Kashmir, India.

Kuthar valley in the Anantnag district of south Kashmir (North-west India) was surveyed to ascertain the prevalence of completed strokes. In a population of 63,645, the survey was from July to November 1986; 91 cases of completed stroke were detected giving a crude prevalence of 143/100,000. Only 10 (10.9%) cases (7W: 3M) were in the age group 15-39 years, a prevalence rate of 41/100,000.

Adolescent↗

Sequential 1H NMR assignment and secondary structure determination of salmon calcitonin in solution.

Salmon calcitonin (sCT) has been investigated by NMR at 500 MHz in a 90% DMSOd6-10% 1H2O (v/v) mixture at 278 K. All backbone and side-chain resonances of the hormone have been assigned by using high-resolution phase-sensitive two-dimensional techniques. Analysis of the type and magnitude of the observed sequential nuclear Overhauser effects, the NH-alpha CH spin-spin coupling constants, and the 1H/2H exchange kinetics measured in 80% DMSOd6-20% 2H2O (v/v) at 278 K enabled prediction of the secondary structure. Overall, an extended conformation is the dominant feature of the solution, but there are clear indications for a short double-stranded antiparallel beta sheet in the central region comprising residues 12-18, connected by a three-residue hairpin loop formed by residues 14-16. Two tight turns, made by residues 6-9 and 25-28, were also identified, but no evidence was found for the presence of a regular helical segment. The beta sheet favors an amphipathic distribution of the residues, orienting the predominantly hydrophilic Ser13, Glu15, and His17 side chains above the plane of the sheet, and the predominantly hydrophobic Leu12, Gln14, and Leu16 below it. This is interpreted as the "seed" of the amphipathic alpha helix postulated to be responsible for the interaction of sCT with lipids, a situation reminiscent of the folding mechanism of signal peptides in the interaction with membranes. The possible significance of the cis-trans Pro23 isomerism is discussed.

Amino Acid Sequence↗

Bioactive conformation of linear peptides in solution: an elusive goal?

Bioactive peptides of natural origin have, in general, short linear sequences, and are characterized by a large conformational flexibility. It is very difficult to study their conformation in solution since they exist, almost invariably, as a complex mixture of numerous conformers, most of which are extended. The so-called bioactive conformation may be one of them, although the solvents used in solution studies often have properties drastically different from those of the biological system in which the peptide acts. There is, however, no simple way of identifying the bioactive conformation amid the many existing conformers. It is possible to approach a solution to this problem using two distinct strategies: (a) Limiting the conformational freedom of the peptide, e.g., by increasing the viscosity of the solution and decreasing the temperature, in the assumption that the bioactive conformation is, even slightly, more stable than the others. (b) Trying to mimic in solution the physicochemical features of the more reliable receptor models. These two approaches will be illustrated with examples taken mainly from opioid peptides.

Amino Acid Sequence↗

Conformational analysis of peptide T and of its C-pentapeptide fragment.

The synthetic peptide of sequence H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, termed peptide T, a competitor of the Human Immunodeficiency Virus in the binding to human T cells, and its C-terminal pentapeptide fragment, were studied by 1H-nmr in DMSO solution to determine conformational preferences. The observation of nuclear Overhauser enhancements (NOEs) for both peptides, and unusual finding for small linear peptides, allowed complete sequence-specific resonance assignments. Long-range NOEs, ring-current shifts, and the very small temperature coefficient of the Thr8 NH chemical shift suggest, for the zwitterionic form of peptide T, the presence in solution of a beta-turn involving Thr5, Asn6, Tyr7 and Thr8. This conformational feature is consistent with previous structure-activity relationship studies indicating the invariance of the same residues in several potent pentapeptide analogues. The studied pentapeptide fragment, although less structured, shows some tendency to fold even in a polar solvent such as DMSO. Preliminary chemotaxis data on some pentapeptide analogues are consistent with our structural model.

HIV↗

Cerebrovascular disease in rural Kashmir, India.

We studied the Kuthar Valley in the Anantnag District of south Kashmir (northwestern India) during the year 1986 to ascertain the prevalence and pattern of completed stroke. We detected 91 cases, giving a crude prevalence rate of 143/100,000. However, age-specific prevalence was 41/100,000 in the group aged 15-39 years and 630/100,000 in the group aged greater than or equal to 40 years; 69.23% of the cases were in men. Hypertension was present in 58.24% of the cases, while strokes due to valvular heart disease and puerperium-related strokes were most common in the young. Our study is first of its kind in this part of India.

Adolescent↗

[The effect of cholecystectomy intervention on the symptomatology in patients with biliary lithiasis].

A series of 298 patients subjected to cholecystectomy ten or more years after surgery is considered. The symptoms of operated patients were analysed clinically so as to establish the possibility that surgery might resolve the symptomatology that had brought the patient to the operation. After profound analysis of the symptomatological variations observed, it is concluded that the dyspeptic syndrome so frequently reported by the patients examined is connected with lithiasic disease and that the operation has different effects on the different symptoms considered.

Adult↗

A 500 MHz study of peptide T in a DMSO solution.

Peptide T, an octapeptide of sequence ASTTTNYT that binds to human T cells, was studied as a zwitterion in DMSOd6 solution by means of proton NMR spectroscopy at 500 MHz. The unusual dispersion of the resonances of residues of the same type (T) makes it possible to assign all resonances to specific residues by means of several 2D techniques. The non-random nature of the conformation is substantiated by the observation of sequential nuclear Overhauser enhancements (NOEs). The low value of the temperature coefficient of the chemical shift of the NH of T8 and a diagnostic NOE between the NHs of T7 and T8 hint that a beta-turn including T5, N6, Y7 and T8 is a prominent conformational feature in solution. The ring current high field shifts of the methyl group and of the NH of T8 are consistent with an interaction with the side-chain of Y7, favoured by the beta-turn.

Dimethyl Sulfoxide↗

Clinical significance of cross-linked fibrin degradation products in essential mixed cryoglobulinemia.

Cross-linked fibrin degradation products (XDP) were measured with a highly sensitive and specific ELISA in 21 patients with essential mixed cryoglobulinemia (EMC) and in 16 controls. Patients had significantly increased levels of XDP, together with abnormalities in routine coagulation tests. Moreover, XDP were higher in patients with more severe disease. These results support the hypothesis that EMC patients have a chronic disseminated intravascular coagulation (DIC), and underline the significance of XDP measurement in the evaluation of these patients.

Adult↗

Complete assignment of the aromatic proton magnetic resonance spectrum of the kringle 1 domain from human plasminogen: structure of the ligand-binding site.

The kringle 1 domain of human plasminogen has been investigated by 1H NMR spectroscopy at 300 and 600 MHz on the basis of a fragment obtained via controlled proteolysis of the zymogen with Staphylococcus aureus V8 protease. The aromatic spectrum has been fully analyzed and all resonances assigned. The Tyr ring signals were identified by reference to the recently reported spectra of the plasminogen kringle 4 homologues from human, bovine, and porcine origin [Ramesh, V., Gyenes, M., Patthy, L., & Llinás, M. (1986) Eur. J. Biochem. 159, 581-595]. In particular, Tyr74 was assigned on the basis of a proton Overhauser experiment showing cross-relaxation with the Trp-II (Trp62) indole ring, a connectivity previously observed in all the kringle 4 variants and that clearly represents a conserved feature of the kringle structure. Ligand binding was investigated by monitoring the effects of the antifibrinolytic drugs epsilon-aminohexanoic acid and p-benzylaminesulfonic acid (BASA) on the 1H NMR spectrum of kringle 1. It is observed that although most aromatic resonances are perturbed by ligand presence, the chemical shift response is significantly more marked for Phe36, Trp62, and Tyr72. Proton Overhauser experiments centered on aromatic transitions from these residues reveal efficient cross-relaxation with BASA, which indicates direct contacts between the hydrophobic side chain rings and the ligand hydrocarbon moiety at the binding site. A close interaction is also found between Tyr64 and Try72 which indicates that the residue 64 ring is positioned close to the binding site. Excellent overall agreement is found between the NMR data and the molecular folding of the prothrombin kringle 1 determined crystallographically [Park, C. H., & Tulinsky, A. (1986) Biochemistry 25, 3977-3982]. A structure is proposed here for the kringle 1 lysine-binding site which is based upon the NMR results, the X-ray structure, and computer graphics modeling. It is concluded that although features of the lysine-binding site are common to plasminogen kringles 1 and 4, in kringle 1 the binding site extends beyond the kringle inner loop as it encompasses residues Arg34 and Phe36 as well. Furthermore, it appears that in kringle 1 Arg34 and Asp55 are likely to play a direct role in the ligand-kringle 1 interaction by reinforcing the polarity of the cationic and anionic centers of the side chains of Arg71 and Asp57, which have been implicated to provide the electrostatic charges in kringle 4 that balance those of the ligand dipole at the binding site.

Amino Acid Sequence↗