Biomedical subjects

C Arús

Publications and source records attributed to C Arús.

42 records · Page 3Linked to original sources

PubMed1981

1H-NMR studies on the binding subsites of bovine pancreatic ribonuclease A.

The titration curves of the C-2 histidine protons of an RNAase derivative (a covalent derivative obtained by reaction of bovine pancreatic RNAase A (EC 3.1.27.5) with 6-chloropurine 9-beta-D-ribofuranosyl 5'-monophosphate) were studied by means of 1H-NMR spectroscopy at 270 MHz. The interaction of natural (5'AMP, 5'GMP, 5'IMP) and halogenated purine mononucleotides (cl6RMP, br8AMP) with RNAase A was also monitored by using the same technique. The slight change observed in the pK values of the active centre histidine residues of the RNAase derivative, with respect to those in the native enzyme, can be considered as evidence that the phosphate of the label does not interact directly either with His-12 or 119 in the p1 site, but the p2 site as proposed previously (Parés, X., Llorens, R., Arús, C. and Cuchillo, C.M. (1980) Eur. J. Biochem. 105, 571--579). Lys-7 and/or Arg-10 are proposed as part of the p2 phosphate-binding subsite. The pK values of His-12 and 119 and the shift of an aromatic resonance of the native enzyme found on interaction with some purine nucleotides, can be interpreted by postulating that the interaction of 5'AMP, 5'GMP and 5'IMP takes place not only in the so-called purine-binding site B2R2p1 but also in the primary pyrimidine-binding site B1R1 and p0 of RNAase A.

Animals↗

PubMed1980

The reaction of bovine pancreatic ribonuclease A with 6-chloropurineriboside 5'-monophosphate. Evidence on the existence of a phosphate-binding sub-site.

The chemical modification of bovine pancreatic ribonuclease A by 6-chloropurine 9-beta-D-ribofuranosyl 5'-monophosphate was studied under several reaction conditions. The reaction, at pH 7.3, 40 degrees C and a nucleotide: enzyme molar ratio of 60, showed a high degree of specificity in comparison to those corresponding to the base or the nucleoside. The main derivative was isolated by means of CM-cellulose chromatography. Subtilisin cleavage of this derivative showed that the substitution had taken place in the S-peptide moiety. Tryptic digestion of the S-peptide indicated that a lysine residue had been modified. Enzymatic and physico-chemical considerations showed that the actual site of reaction was the alpha-amino group of Lys-1. The structural and kinetic properties of the derivative are consistent with the existence of a phosphate-binding sub-site near the N-terminal region of the enzyme.

Amino Acids↗

PubMedDate not supplied

Towards a method for automated classification of 1H MRS spectra from brain tumours.

Recent studies have shown that MRS can substantially improve the non-invasive categorization of human brain tumours. However, in order for MRS to be used routinely by clinicians, it will be necessary to develop reliable automated classification methods that can be fully validated. This paper is in two parts: the first part reviews the progress that has been made towards this goal, together with the problems that are involved in the design of automated methods to process and classify the spectra. The second part describes the development of a simple prototype system for classifying 1H single voxel spectra, obtained at an echo time (TE) of 135 ms, of the four most common types of brain tumour (meningioma (MM), astrocytic (AST), oligodendroglioma (OD) and metastasis (ME)) and cysts. This system was developed in two stages: firstly, an initial database of spectra was used to develop a prototype classifier, based on a linear discriminant analysis (LDA) of selected data points. Secondly, this classifier was tested on an independent test set of 15 newly acquired spectra, and the system was refined on the basis of these results. The system correctly classified all the non-astrocytic tumours. However, the results for the the astrocytic group were poorer (between 55 and 100%, depending on the binary comparison). Approximately 50% of high grade astrocytoma (glioblastoma) spectra in our data base showed very little lipid signal, which may account for the poorer results for this class. Consequently, for the refined system, the astrocytomas were subdivided into two subgroups for comparison against other tumour classes: those with high lipid content and those without.

Brain Neoplasms↗

PubMedDate not supplied

Genetic programming for classification and feature selection: analysis of 1H nuclear magnetic resonance spectra from human brain tumour biopsies.

Genetic programming (GP) is used to classify tumours based on 1H nuclear magnetic resonance (NMR) spectra of biopsy extracts. Analysis of such data would ideally give not only a classification result but also indicate which parts of the spectra are driving the classification (i.e. feature selection). Experiments on a database of variables derived from 1H NMR spectra from human brain tumour extracts (n = 75) are reported, showing GP's classification abilities and comparing them with that of a neural network. GP successfully classified the data into meningioma and non-meningioma classes. The advantage over the neural network method was that it made use of simple combinations of a small group of metabolites, in particular glutamine, glutamate and alanine. This may help in the choice of the most informative NMR spectroscopy methods for future non-invasive studies in patients.

Artificial Intelligence↗

PubMedDate not supplied

1H NMR spectroscopy of colon tumors and normal mucosal biopsies; elevated taurine levels and reduced polyethyleneglycol absorption in tumors may have diagnostic significance.

Twenty-three pairs of normal mucosa and colonic adenocarcinoma biopsy specimens have been examined in this pilot study by 1H NMR spectroscopy at 9.4 T to determine whether it was possible to find spectral malignancy markers. The 3.2 ppm (trimethylamine-containing compounds)/0.9 ppm (methyl of fatty acids) resonance intensity ratio in water suppressed spectra, proposed by other authors as a malignancy marker, results in our hands, using resonance areas, in partial overlap between tumor and mucosa values, which reduces its diagnostic value. Furthermore, we have found that submucosa contamination could mask the normal mucosa pattern and artifactually decrease the 3.2/0.9 ppm, ratio value by increasing the 0.9 ppm resonance due to the known triglyceride content of normal submucosa. On the other hand, we have observed in the Hahn spin-echo spectra of intact biopsies resonances arising from taurine and exogenous polyethyleneglycol (PEG). Their assignment and quantification has been carried out in perchloric acid extracts of the tissue biopsies. The taurine (3.4 ppm)/creatine (3.0 ppm) area ratio produced an excellent discrimination between normal mucosa and tumour groups while the PEG (3.7 ppm)/creatine (3.0 ppm) area ratio presented a large overlap, although it was clearly higher in the mucosae than in the tumors for paired samples. These two NMR observable parameters are in our hands highly discriminating and are accordingly proposed as malignancy markers in tissue biopsies although their possible utility for in vivo studies remains to be demonstrated.

Adenocarcinoma↗

PubMedDate not supplied

Study of the ability of proton nuclear magnetic resonance spectroscopy of human plasma to differentiate between controls and breast cancer patients.

Water-suppressed proton nuclear magnetic resonance spectroscopy of plasma had been proposed as a technique for detecting malignant tumors although its general diagnostic value is widely contested. To assess its diagnostic value in screening for breast cancer, we collected and analyzed 108 plasma samples from healthy women and women with breast disorders, mainly adenocarcinomas. No significant differences were found between controls and patients when average methylene-methyl linewidths were compared. Significant differences, however, were observed when methylene linewidths were compared. Unfortunately, the marked overlapping of both groups greatly reduced the possible diagnostic value of the technique. Among the various biochemical parameters analyzed for each plasma sample--triglyceride, total cholesterol and HDL cholesterol concentration, altered levels of carcinoembryonic antigen, phosphohexose isomerase, 5'-nucleotidase and phosphatase alkaline in patient samples, and estrogen and progesterone receptors of tumors--only triglyceride concentrations presented a clear inverse linear correlation with methylene linewidths.

Adenocarcinoma↗