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Biomedical subjects

T Alonso

Publications and source records attributed to T Alonso.

At least 19 recordsLinked to original sources

The Web as an educational tool for/in learning/teaching bioinformatics statistics.

Statistics provides essential tool in Bioinformatics to interpret the results of a database search or for the management of enormous amounts of information provided from genomics, proteomics and metabolomics. The goal of this project was the development of a software tool that would be as simple as possible to demonstrate the use of the Bioinformatics statistics. Computer Simulation Methods (CSMs) developed using Microsoft Excel were chosen for their broad range of applications, immediate and easy formula calculation, immediate testing and easy graphics representation, and of general use and acceptance by the scientific community. The result of these endeavours is a set of utilities which can be accessed from the following URL: http://gmein.uib.es/bioinformatica/statistics. When tested on students with previous coursework with traditional statistical teaching methods, the general opinion/overall consensus was that Web-based instruction had numerous advantages, but traditional methods with manual calculations were also needed for their theory and practice. Once having mastered the basic statistical formulas, Excel spreadsheets and graphics were shown to be very useful for trying many parameters in a rapid fashion without having to perform tedious calculations. CSMs will be of great importance for the formation of the students and professionals in the field of bioinformatics, and for upcoming applications of self-learning and continuous formation.

Computational Biology↗

[Antithrombotic treatment in non-rheumatic atrial fibrillation. Do we follow the recommendations of clinical trials?].

OBJECTIVES: Several clinical trials have demonstrated that antithrombotic treatment may be effective in prevention of stroke in nonrheumatic atrial fibrillation (AF). The aim of this study was to assess if we follow clinical trial recommendations in community practice. METHODS: We analyzed 225 medical records of patients diagnosed of nonrheumatic AF in Cáceres, during February and March 1998. Patients who were contraindicated to follow antiagreggation or anti-coagulation treatment were excluded. We compared patients with and without antithrombotic treatment with different demographic characteristics and embolic risk factors. RESULTS: 205 patients were included in the study, 149 (72.6%) had high embolic risk. 62 (30.2%) followed anticoagulation, 94 (45.8%) antiaggregation treatment, 5 (2.4%) both treatment and 49 (24%) were not receiving therapy. We didn't findings differences between age, sex, presence of ischemic heart disease, hypertension and congestive heart failure in last three months compared with the patients in respect to the group of patients with anticoagulation and antiaggregation therapy or without it. We determinate as well that previous stroke and echocardiographical finds (valve disease, valve calcification, ventricular dysfunction) were more frequent in the anticoagulation and antiaggregate patients than in those without therapy. CONCLUSION: A high range of nonrheumatic AF patients take any kind of antithrombotic preventive therapy, though a great number of patients with high embolic risk could still get benefits from anticoagulation therapy. We should considerate in the therapy assessment some other clinical characteristics as hypertension, isquemic heart disease and heart failure apart from echocardiographical findings.

Aged↗

Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990).

From January 1979 to December 1990 we studied the susceptibility of 1,492 pneumococcal strains isolated from adult patients in Bellvitge Hospital, Barcelona, Spain, to nine antimicrobial agents. Among clinically significant pneumococci, the incidence of penicillin-resistant strains increased from 4.3% in 1979 to 40% in 1990, and that of erythromycin-resistant strains also rose from 0% in 1979 to 9.4% in 1990. On the other hand, the incidence of strains resistant to tetracycline decreased from 76.1% to 37.6%, as did that of chloramphenicol-resistant strains, from 56.5% to 29.4%. The incidence of co-trimoxazole-resistant strains was about 40% throughout the study. Even more alarming was the finding that about 70% of penicillin-resistant strains showed multiple resistance to non-beta-lactam antibiotics. All pneumococci were susceptible to vancomycin, and all but six were susceptible to rifampin. We observed that isolates from cerebrospinal fluid and the respiratory tract were significantly more resistant to penicillin than were isolates from blood. The majority of strains (95%) belonged to serogroups or serotypes included in the 23-valent pneumococcal vaccine and 77.6% of penicillin-resistant strains belonged to groups 23, 6, 9, and 19.

Adult↗

Decreased susceptibility of penicillin-resistant pneumococci to twenty-four beta-lactam antibiotics.

The in-vitro activity of 24 beta-lactam antibiotics was compared using three groups of pneumococci and an agar dilution method comprising 100 penicillin-susceptible, 100 intermediately penicillin-resistant, and 100 highly penicillin-resistant pneumococcal strains. Our results show that intermediately penicillin-resistant and highly penicillin-resistant pneumococci had decreased sensitivity to other beta-lactam agents. According to their relative in-vitro activity, the antimicrobials were classified into three groups. The first group included drugs more active than penicillin (imipenem, meropenem, cefotaxime, ceftriaxone, and cefpirome), which could be useful for the treatment of infections due to penicillin-resistant strains. The second group showed slightly lesser activity than did penicillin, and included: ampicillin, cefdinir, cefuroxime, cefoperazone, azlocillin, mezlocillin, piperacillin, cephalothin, and cefamandole. The remaining antibiotics (oxacillin, cefixime, ceftizoxime, cefetamet, cefaclor, ceftazidime, cefoxitin, cefonicid, and latamoxef) showed poor activity against penicillin-resistant strains, precluding their use for empirical treatment in areas with a high prevalence of penicillin-resistant strains.

Anti-Bacterial Agents↗

Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients.

Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population.

Adult↗

Increased intracellular glycerophosphoinositol is a biochemical marker for transformation by membrane-associated and cytoplasmic oncogenes.

Transformation of rodent fibroblasts by cytoplasmic (mos, raf) and membrane-associated (ras, src, met, trk), but not nuclear (myc, fos) oncogenes results specifically in a very significant elevation of intracellular levels of glycerophosphoinositol (GPI). This elevation is specifically associated with the transformed state of the cells and not merely with their active state of proliferation. The basal phospholipase A2 (PLA2) activity of the same cells is also significantly stimulated in vivo. Our results are consistent with the notion that the elevated levels of GPI result from deacylation of lysophosphatidylinositol released by the enhanced PLA2 activity. GPI is a water-soluble, easily detectable metabolite which may constitute a convenient biochemical marker for malignant transformation by this particular group of oncogenes.

Animals↗

Alterations of G-protein coupling function in phosphoinositide signaling pathways of cells transformed by ras and other membrane-associated and cytoplasmic oncogenes.

We showed previously that transformation by cytoplasmic and membrane-associated oncogenes including ras results in uncoupling between surface stimulation by platelet-derived growth factor, bombesin, and serum and activation of intracellular phospholipase C (PLC); this uncoupling does not involve alterations at the receptor or effector enzyme levels (T. Alonso, R. O. Morgan, J. C. Marvizon, H. Zarbl, and E. Santos, Proc. Natl. Acad. Sci. USA 85:4271-4275, 1988). In this study, we stimulated normal and oncogene-transformed NIH 3T3 cells with fluoroaluminate (AIF4-), thus directly activating PLC-associated G protein(s) and bypassing the receptor step. A1F4(-)-elicited PLC responses were significantly impaired in transformed cells when compared with those in their normal counterparts, suggesting that the uncoupling of PLC is the result, at least in part, of functional impairment at the G-protein level. Transformation by ras oncogenes has also been reported to result in enhanced PLC response to bradykinin resulting from increased receptor numbers (G. Parries, R. Hoebel, and E. Racker, Proc. Natl. Acad. Sci. USA 84:2648-2652, 1987; J. Downward, J. de Gunzburg, R. Riehl, and R. Weinberg, Proc. Natl. Acad. Sci. USA 85:5774-5778, 1988). We demonstrate here that transformation by other membrane-associated and cytoplasmic oncogenes also results in increased responsiveness to bradykinin ("supercoupling") and enhanced receptor numbers. However, there is no direct correlation between the number of receptors and the enhancement in responsiveness, suggesting that other factors besides receptor number are also involved in the enhanced responses. We propose that a common effect of transformation by cytoplasmic and membrane-associated oncogenes is functional alteration of coupling G proteins and that a similar modification of different kinds of G proteins may account for the pleiotropic alterations of signal transduction (uncoupling and supercoupling) observed.

Aluminum↗

Preparation, characterization and properties of monoclonal antibodies against intact H-ras p21 proteins.

Monoclonal antibodies against intact normal (Gly12) and transforming (Lys12) BALB p21 ras proteins have been prepared and characterized. Their reactivity against the purified antigen proteins as well as against cellular ras proteins present in cell lines transformed by various alleles of ras genes was determined. Although some of the antibodies recognized preferentially either the normal or the activated form of BALB p21, none of them recognized exclusively either one. Deletion fragments of Ha-ras proteins were used in ELISA to determine the region of the protein encompassing the epitope recognized by each antibody. Two regions (amino acid stretches 23-69 and 89-106) accounted for the epitopes of about 75% of the mAbs raised in this study, suggesting that they encompass the most exposed and immunogenic domains in native ras p21 proteins. The affinity of these antibodies for p21 was higher than that of other ras mAbs described previously and allowed for (i) more quantitative immunoprecipitation of ras proteins, (ii) the use of selected mAbs in immunoaffinity purification of ras proteins and (iii) improved immunohistochemical detection of p21 in fixed tissues (Ward et al., accompanying manuscript). Finally, one of the mAbs described here appeared to recognize specifically a related antigenic molecule besides ras p21.

Animals↗

Malignant transformation by ras and other oncogenes produces common alterations in inositol phospholipid signaling pathways.

The role of ras proteins in signal transduction was assessed by studying inositol phospholipid metabolism and inositol phospholipid-mediated cellular responsiveness to agonists in cells transformed by ras and other oncogenes. Specific alterations were observed in the inositol phospholipid cycle of ras-transformed fibroblasts, but similar changes were also produced by spontaneous transformation or transformation mediated by either membrane-associated oncogenes, such as src, met, or trk, or cytoplasmic oncogenes, mos and raf; the nuclear oncogenes fos and myc did not produce these changes. The alterations included (i) stimulation of phospholipase A2 activity as indicated by elevated levels of glycerophosphoinositol and nonesterified arachidonic acid and (ii) specific uncoupling between surface receptor-mediated stimulation by platelet-derived growth factor, bombesin, or serum and activation of intracellular phospholipase C. These findings suggest the existence of common biochemical pathways for transformation by cytoplasmic and membrane-associated oncogenes and are not consistent with the hypothesis that 21-kDa ras proteins (p21) are direct or distinct regulatory elements of phospholipase C or phospholipase A2 in inositol phospholipid signal transduction pathways.

Animals↗

Regional changes of brain Na+,K+-transporting adenosine triphosphatase related to ovarian function.

Synaptosomal Na+,K+-transporting ATPase activity of the mediobasal hypothalamus (MBH), the medial preoptic-suprachiasmatic (POSC) region and cerebral cortex was measured in rats at different stages of the estrous cycle and after ovariectomy and estradiol replacement. Enzyme activity of the MBH and POSC showed cyclic changes. In both regions it increased shortly before the proestrus surge of LH. However, the two areas responded to castration and estrogen treatment in an opposite fashion. No changes were detected in enzyme activity in the cerebral cortex. These findings are consistent with previous reports on cyclic changes in electrical activity and suggest that Na+,K+-ATPase activity could be a useful indicator of neural activity for the study of neuroendocrine interactions.

Animals↗

[Our experience with Kufs disease: familial form and sporadic case].

Our experience on Kufs' disease includes a familiar, neurovisceral form and a sporadic case. The familiar form shows an autosomal, dominant inheritance, and belongs to Berkovic's type B. A variability on the age of onset was observed, being more protracted in women. The sporadic case belongs to Berkovic's type A. Her EEG showed a periodic, short-interval, activity for a long period of illness. NMR findings were nonspecific for the diagnosis. All cases showed granular osmiophilic deposits, but not storage characterized by fingerprint profiles. Visceral storage in many cases on Kufs' disease suggests the utility of visceral biopsy evaluation for the diagnosis during life.

Adult↗