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Biomedical subjects

C Martín

Publications and source records attributed to C Martín.

At least 91 records · Page 5Linked to original sources

Paediatric Hodgkin's disease in Spain: association with Epstein-Barr virus strains carrying latent membrane protein-1 oncogene deletions and high frequency of dual infections.

The present report analyses the distribution of 30-base pair (bp) latent membrane protein-1 (LMP-1) oncogene deletions in 24 cases of Epstein-Barr virus (EBV)-positive paediatric Hodgkin's disease (HD) and 39 normal controls. The 30 bp deletion was identified in 19/24 paediatric HD cases (79.2%), of which seven (29.2%) showed the deleted fragment alone, whereas in the remaining 12 (50%) it was accompanied by the nondeleted fragment. Conversely, the deletion was found in 8/22 (36.4%) EBV-positive healthy children, in two (9.1%) of whom the deleted fragment was alone, and was coinfecting with the nondeleted fragment in the other six (27.3%). The LMP-1 deletion was significantly associated with paediatric HD, both including dual infections (P=0.006) or excluding them (P=0.01). Type 2 EBV was carried by 25% of HD children, whereas all controls harboured type 1 EBV. The 30 bp deletion was present in all the paediatric HD specimens that contained type 2 EBV, suggesting that a deleted type 2 EBV strain may be more tumourigenic than a nondeleted type 2 EBV strain. These findings indicate that EBV strains carrying a 30 bp deletion in the third exon of the LMP-1 oncogene may have a more important role in the pathogenesis of paediatric HD than full-length EBV strains. Dual infection by LMP-1 deleted and nondeleted EBV strains is a frequent event both in healthy children and in the paediatric HD population.

Child, Preschool↗

Molecular cloning and characterization of Tap, a putative multidrug efflux pump present in Mycobacterium fortuitum and Mycobacterium tuberculosis.

A recombinant plasmid isolated from a Mycobacterium fortuitum genomic library by selection for gentamicin and 2-N'-ethylnetilmicin resistance conferred low-level aminoglycoside and tetracycline resistance when introduced into M. smegmatis. Further characterization of this plasmid allowed the identification of the M. fortuitum tap gene. A homologous gene in the M. tuberculosis H37Rv genome has been identified. The M. tuberculosis tap gene (Rv1258 in the annotated sequence of the M. tuberculosis genome) was cloned and conferred low-level resistance to tetracycline when introduced into M. smegmatis. The sequences of the putative Tap proteins showed 20 to 30% amino acid identity to membrane efflux pumps of the major facilitator superfamily (MFS), mainly tetracycline and macrolide efflux pumps, and to other proteins of unknown function but with similar antibiotic resistance patterns. Approximately 12 transmembrane regions and different sequence motifs characteristic of the MFS proteins also were detected. In the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), the levels of resistance to antibiotics conferred by plasmids containing the tap genes were decreased. When tetracycline accumulation experiments were carried out with the M. fortuitum tap gene, the level of tetracycline accumulation was lower than that in control cells but was independent of the presence of CCCP. We conclude that the Tap proteins of the opportunistic organism M. fortuitum and the important pathogen M. tuberculosis are probably proton-dependent efflux pumps, although we cannot exclude the possibility that they act as regulatory proteins.

Amino Acid Sequence↗

Allele-specific PCR method based on pncA and oxyR sequences for distinguishing Mycobacterium bovis from Mycobacterium tuberculosis: intraspecific M. bovis pncA sequence polymorphism.

An allele-specific amplification method based on two genetic polymorphisms to differentiate Mycobacterium tuberculosis from Mycobacterium bovis was tested. Based on the differences found at position 169 in the pncA genes from M. tuberculosis and M. bovis, a PCR system which was able to differentiate most of the 237 M. tuberculosis complex isolates tested in one of the two species was developed. All 121 M. tuberculosis strains showed the expected base (cytosine) at position 169. Most of the M. bovis isolates had a guanine at the cited position. Nevertheless, 18 of the 116 M. bovis isolates, all of them goat isolates, showed the pncA polymorphism specific to M. tuberculosis. These results suggest that goat M. bovis may be the nicotinamidase-missing link at the origin of the M. tuberculosis species. Based on the polymorphism found at position 285 in the oxyR gene, the same system was used to differentiate M. tuberculosis from M. bovis. In this case, DNAs from all 121 M. tuberculosis isolates had the expected base (guanine) at this position. In addition, all 116 M. bovis isolates, including those from goats, showed the identical polymorphism (adenine). The oxyR allele-specific amplification method can differentiate M. bovis from M. tuberculosis, is rapid (results can be obtained in less than 3 h), and is easy to perform.

Alleles↗

Organizing pneumonia in textile printing workers: a clinical description.

In April 1992 an outbreak of severe respiratory illness occurred among aerographic textile workers in the area of Alcoi, Autonomous Community of Valencia, Spain. An epidemiological study linked this outbreak to the use of a reformulated aerosolized product, Acramin-FWN. We analyzed clinical, laboratory, and pathological data of the first 14 patients with confirmed organizing pneumonia (OP) secondary to this newly recognized occupational toxicant. The mean age of the patients was 30 yrs. The most common clinical findings were cough (86%), epistaxis (71%), dyspnoea (64%), oppressive chest pain (57%), and crackles (50%). A restrictive functional pattern was evident in 64%. Radiographic findings consisted predominantly of patchy infiltrates in 65% and a micronodular pattern in 35%. Treatment with corticosteroids did not prevent initial progression in 11 of the 14 patients and development of irreversible respiratory failure in five patients. At necropsy, besides features of OP, interstitial fibrosis and diffuse alveolar damage were evident. A low total lung capacity, the presence of crackles at admission, and increases in the alveolar-arterial oxygen difference were predictive of death. The organizing pneumonia caused by the inhalation of Acramin-FWN is characterized by a tendency to evolve into progressive interstitial fibrosis despite the use of corticosteroids. The illness is restricted to the respiratory system and once respiratory failure has developed the prognosis is poor.

Adipates↗

Chylothorax in cirrhosis of the liver: analysis of its frequency and clinical characteristics.

OBJECTIVES: To ascertain the frequency and to describe the clinical and biochemical features of cirrhotic chylothorax. DESIGN: A descriptive clinical study. SETTING: A community teaching hospital. PATIENTS AND METHODS: Since November 1989 to October 1995, 809 patients with pleural effusions were studied by thoracentesis. Pleural effusions with a concentration of triglycerides higher than 110 mg/dL, a pleural fluid to serum triglyceride ratio higher than 1, and a pleural fluid to serum cholesterol ratio lower than 1 were considered chylothorax. RESULTS: Twenty-four patients had pleural effusions that complied with all three aforementioned biochemical conditions. Five of these 24 patients (20%), were found to have liver cirrhosis as the main cause of chylothorax and in 3 of them, an abdominal source of the effusion could be demonstrated by intraperitoneal injection of a radioisotope (99mTc-sulfur colloid). The cirrhotic chylous effusions had significantly lower (p<0.005) protein (median, 1.7; range, 1.4 to 2.7 g/dL), lactate dehydrogenase (LDH) (median, 96; range, 77 to 138 IU/L), and cholesterol (median, 25; range, 22 to 64 mg/dL) levels than chylous effusions resulting from other causes (protein: median, 4.1; range, 1.7 to 6.8 g/dL; LDH: median, 351; range, 140 to 8,600 IU/L; and cholesterol: median, 87; range, 38 to 160 mg/dL). Cirrhotic chylothorax was always a transudate according to Light's criteria. CONCLUSIONS: Chylothorax is a rare and apparently underappreciated manifestation of cirrhosis resulting from transdiaphragmatic passage of chylous ascites. Its uniform biochemical characteristics can facilitate its separation from chylous effusions of different etiology, therefore avoiding potentially harmful diagnostic and therapeutic procedures.

Adult↗

Solubilization and interaction of sulindac with polyvinylpyrrolidone K30 in the solid state and in aqueous solution.

In this report the interactions of sulindac with polyvinylpyrrolidone K30 (PVP K30), both in the solid state and in aqueous solution, have been investigated. Solid dispersions of sulindac with PVP K30 were prepared by the solvent method in ethanol from various drug-to-polymer weight ratios. X-ray powder diffraction and differential scanning calorimetry have shown that PVP inhibits the crystallization of sulindac. The stabilization of the noncrystalline state of sulindac was shown by x-ray diffractometry after a 1-year storage. There was a considerable increase in the release rate of the drug when the polymer content was increased and the intrinsic dissolution rate values of these systems were calculated. From the UV spectra a bathochromic shift and a well-defined isosbestic point were observed at pH 2 and 6, which confirmed an interaction between the drug and the polymer in solution. Moreover, the apparent solubility of sulindac has been modified as a function of the polymer concentrations. The binding process between the drug and PVP was exothermic from the stability constant values at 25, 30, and 37 degrees C at pH 2.

Calorimetry, Differential Scanning↗

Solubilization and interaction of sulindac with beta-cyclodextrin in the solid state and in aqueous solution.

A sulindac-beta-cyclodextrin complex was obtained by the coprecipitation method. Kneaded solids and physical mixtures were also prepared. The complex was shown by x-ray powder diffraction to be noncrystalline whereas pure drug and any of the other sulindac-beta-CD system were crystalline. the endothermic peak of sulindac due to the fusion of drug disappeared in DSC thermograms for the coprecipitate product, which confirmed the interaction between sulindac and beta-CD in the solid state. After a 1-year storage drug crystals could not be observed by x-ray diffractometry, which indicated that the complex formed was stable. The complex showed the fastest dissolution rate which might be attributed to the high-energy noncrystalline state and the inclusion complex formation in solution. UV spectra were modified and the apparent solubility of the drug increased with the addition of beta-CD, which confirmed the interaction between sulindac and the ligand in solution. The apparent stability constant, K1:1, for the complex at pH 2 and 25, 30, and 37 degrees C was 340, 220, and 160 M-1, respectively, which confirmed the influence of temperature on the complex stability. The value of K1:1 at pH 6 and 25 degrees C was 139 M-1, which indicated that the complex is formed easier with the non-ionized sulindac. The enthalpy change, delta H degree, showed that the binding process is exothermic.

Chemical Phenomena↗

Importance of mixed chimerism to predict relapse in persistently BCR/ABL positive long survivors after allogeneic bone marrow transplantation for chronic myeloid leukemia.

Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitative RT-PCR is of limited value in predicting disease progression for individual patients. We have studied the chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors, persistently bcr/abl positive by RT-PCR. The median age of the series was 31 years (18-49) and disease status at BMT was: chronic phase: 11, accelerated phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled transprobe-1. PCR analysis of chimerism was assessed using primers for the following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52. Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen patients showed complete chimerism and lacked BCR rearrangement over time by Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent BCR rearrangement was observed in these 2 patients from +12 and +11 months respectively. Our data suggest that mixed chimerism may predict hematologic or cytogenetic relapse by several months in those patients who are persistently PCR-positive post-BMT.

Adult↗

In vitro inhibition by estrogens of the oxidative modifications of human lipoproteins.

Estrogens exert protective actions against atherosclerosis, part of these effects having been ascribed to their antioxidant properties. The aim of this work was to assess the ability of estrogens to prevent the oxidative modifications of low density lipoproteins (LDL) and other plasma lipoprotein fractions whose relationship with atherosclerosis has been less studied. For this purpose, different estrogen compounds were used: natural and synthetic estrogens, and catecholestrogens. The molecules were added in vitro to human LDL and very low density lipoproteins (VLDL) in the presence of Cu2+. The lipoprotein oxidative modifications were determined by measuring the formation of thiobarbituric acid reactive substances, the appearance of conjugated dienes and the degradation of tryptophan groups from the apoproteins. In VLDL, 2-hydroxyestradiol and diethylstilbestrol exerted potent antioxidant effects similar to those found for alpha-tocopherol and probucol. 17beta-Estradiol and 4-hydroxyestradiol also prevented VLDL oxidation, but to a lesser extent. When LDL were used, estrogens similarly exerted antioxidant actions, 2-hydroxyestradiol being the most potent inhibitor. These results show that estrogens, whose antioxidant actions have been demonstrated in other experimental models, also possess the ability to prevent in vitro the oxidative modifications of human plasma LDL and VLDL.

Cholesterol↗

The molecular epidemiology of tuberculosis in Zaragoza, Spain: a retrospective epidemiological study in 1993.

SETTING: The incidence of tuberculosis (TB) in Spain is one of the highest in Europe. In Zaragoza region the incidence rate of tuberculosis and the acquired immune deficiency syndrome (AIDS) are close to the national average. OBJECTIVE: To better define the molecular epidemiology of tuberculosis in an area of Europe where this has not been previously studied. DESIGN: A retrospective epidemiological study on tuberculosis was conducted in Zaragoza, a region of Spain, in 1993. The study population consisted of 226 patients from whom positive culture and complete clinical and demographic data were available. Mycobacterium tuberculosis strains were typed by standard restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns when five or more copies of IS6110 are present. The 137 non-clustered patients were compared with the 89 clustered patients and studied by using univariate analysis. RESULTS: Thirty-nine percent of the patients were clustered, suggesting possible recent transmission. Infection with drug-resistant M. tuberculosis was associated with a decreased risk of being in a cluster. The strains isolated from human immunodeficiency virus (HIV)-positive patients were not associated with clustering. We found that immigration was not a major determinant in the total number of TB cases. CONCLUSION: Immigration, HIV and drug resistance were not associated with recent transmission. More than 50% of the clusters contained two or three patients, indicating that small outbreaks were responsible for most of the tuberculosis cases. Our RFLP typing results indicate that a TB control programme should be implemented in Spain in order to lower transmission of TB.

AIDS-Related Opportunistic Infections↗

Tuberculous pleurisy with or without radiographic evidence of pulmonary disease. Is there any difference?

SETTING: A community teaching hospital in Alicante, Spain. OBJECTIVE: To assess the characteristics of tuberculous pleurisy (TP) in our hospital, and to evaluate the differences between primary and reactivation forms. DESIGN: Between January 1984 and December 1993, all human immunodeficiency virus (HIV)-negative patients with TP were included in the study. From September 1987 onward, patients were prospectively studied. Charts, radiography, pleural fluid findings and diagnostic methods were evaluated. Two groups were distinguished according to chest radiographs: those patients with upper lobe lesions, calcified adenopathy and old pleural thickening were considered reactivation forms. RESULTS: Of the 129 patients (mean age, 31 +/- 18 years), 76% had primary TP and 24% reactivation TP. Differences were found in age (28 +/- 17 vs 40 +/- 18 years, P < 0.01), smoking (43% vs 74%, P < 0.01) and alcohol abuse (23% vs 47%, P < 0.05), weight loss (29% vs 50%, P < 0.05), positive sputum smears and cultures (2% vs 16%, 7% vs 28%, P < 0.01), and number of large effusions (46% vs 26%, P < 0.05), but not in tuberculin reactivity, pleural fluid findings, positive pleural cultures, or presence of pleural granuloma. CONCLUSION: In our setting, TP predominantly affects young adults. Clinical, immunological, and pleural findings are similar to those of patients with classic symptoms of TP. Older age, smoking and alcohol abuse, smaller effusions and sputum yield are differential characteristics of reactivation forms.

Adult↗

Inhibition by estrogens of the oxidant-mediated mobilization of arachidonic acid in hepatocytes.

Oxidative stress is associated with alterations in arachidonic acid (AA) metabolism. The present work was performed to assess the effect of the oxidant tert-butyl hydroperoxide on the release of AA from rat hepatocytes, and the possible preventive actions of estrogens on this effect. The exposure of [14C]-prelabeled cells to tertbutyl hydroperoxide produced the mobilization of [14C]-AA from hepatocyte lipids, both an intracellular [14C]-AA accumulation and an increased release of [14C]-products into the medium being observed. The formation of lysophospholipids was also enhanced significantly in the presence of the oxidant, thus suggesting the involvement of phospholipase A2 (E.C. 3.1.1.4) in the hepatocyte response to tert-butyl hydroperoxide. Estradiol and 2-hydroxyestradiol (25-100 microM) added in vitro to cell suspensions prevented significantly the oxidant- mediated stimulation of AA release, this effect probably being caused by the estrogen inhibitory actions against cellular lipid peroxidation.

Animals↗

[Positron emission tomography detection of residual disease in a case of lung cancer].

To date, computed tomography is considered the best procedure to detect either relapse or residual disease in non-small cell lung cancer. However, in recent years several studies have stressed the value of F-18 fluorodeoxyglucose positron emission tomography (FDG PET) which takes advantage of the enhanced glucose uptake observed in neoplastic cells. We present the case of a patient with a locally advanced non-small cell lung cancer who received trimodal treatment with induction chemotherapy followed by surgical resection and postoperative irradiation and lately developed brain metastases which were treated with chemoradiotherapy plus radiosurgery. However a small residual lesion remained in the brain magnetic resonance. Such abnormality was evaluated by means of FDG PET which did not show any increase on FDG uptake. The present case prompt us to review the role of FDG PET as a procedure that enable to detect subclinical disease and its potential usefulness taking into account the improvement in management strategies that has been attained in non-small cell lung cancer.

Adult↗