Biomedical subjects

L Esteban

Publications and source records attributed to L Esteban.

16 recordsLinked to original sources

PubMed2000

The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties.

Targeted disruption of both alleles of mouse sos1, which encodes a Ras-specific exchange factor, conferred mid-gestational embryonic lethality that was secondary to impaired placental development and was associated with very low placental ERK activity. The trophoblastic layers of sos1(-/-) embryos were poorly developed, correlating with high sos1 expression in wild-type trophoblasts. A sos1(-/-) cell line, which expressed readily detectable levels of the closely related Sos2 protein, formed complexes between Sos2, epidermal growth factor receptor (EGFR) and Shc efficiently, gave normal Ras.GTP and ERK responses when treated with EGF for < or =10 min and was transformed readily by activated Ras. However, the sos1(-/-) cells were resistant to transformation by v-Src or by overexpressed EGFR and continuous EGF treatment, unlike sos1(+/-) or wild-type cells. This correlated with Sos2 binding less efficiently than Sos1 to EGFR and Shc in cells treated with EGF for > or =90 min or to v-Src and Shc in v-Src-expressing cells, and with less ERK activity. We conclude that Sos1 participates in both short- and long-term signaling, while Sos2-dependent signals are predominantly short-term.

Animals↗

PubMed2000

[The treatment and prognosis of sarcoidosis. Apropos 53].

OBJECTIVE: We retrospectively studied 53 cases of sarcoidosis which have been diagnosed at our service during de last 14 years. The criteria for starting therapy with corticosteroids and recurrences were analyzed. METHOD: The patients mean (SD) age was 42 (15) years old (range 16-76) and the majority were female (72%). 15 patients (28.3%) received corticosteroids. The only differences with respect to patients not treated were the presence of respiratory symptoms (47% vs 18%; p = 0.04) and the abnormality of spirometric parameters (DLCO/VA p = 0.01; CV p = 0.002). RESULTS: 17 (32%) patients recurred. 14 (82%) of them required corticosteroids. This percentage was significantly greater than that of patients treated at first episode (82% vs 28%, p = 0.0002). All patients improved with treatment. The only difference with respect to patients without recurrences were to be treated at the first episode (53% vs 17%, p = 0.007).

Adrenal Cortex Hormones↗

PubMed1999

Metabolism of the complex monofluorophosphate-alpha 2-macroglobulin in the rat.

Sodium monofluorophosphate (MFP) is a drug used in the treatment of primary osteoporosis. Following the intake of MFP, a small fraction of the drug is absorbed intact and forms a complex with alpha 2-macroglobulin (MFP-alpha 2M) inactivating the antiproteasic activity of the globulin. The complex has been shown to occur in the serum of rats and human being. This paper reports data on the metabolism of this complex in the rat. In vitro experiments showed that liver and bone tissue remove MFP-alpha 2M from the incubation medium. When the experiments were pursued beyond the time needed to reduce the complex concentration to very low levels, fluorine (F) reappears in the medium in two forms: bound to low molecular weight macromolecule/s (2,200 +/- 600 Da) and as ionic F. Concentrations of these F fractions increase while that of the complex decreases as a function of time. In vitro, uptake of the complex by liver or bone tissue was not affected by the presence of colchicine or methylamine. These drugs, however, inhibited intracellular metabolism of the complex, as indicated by the impairment of the return of F species to the extracellular space and the increase in F content of the tissue. The cellular receptors responsible for the uptake of the complex in liver and bone are insensitive to low concentration of calcium and inhibited by polyinosinic acid[5']. These features characterize the "scavenger" receptor, one of the two receptor types known to remove inactive alpha 2M from the circulation. Injection of polyinosinic acid [5'] to living rats also hindered the disappearance of the complex from serum. It is concluded that the metabolism of the MFP-alpha 2M complex involves binding to receptors, uptake by cells, lysosomal degradation and return of F bound to low molecular weight macromolecule/s to the extracellular space. It is assumed, however, that inorganic F is the final product of lysosomal hydrolysis of the protein moiety.

Animals↗

PubMed1997

Binding of monofluorophosphate to alpha2-macroglobulin and C3.

After administering an oral dose of monofluorophosphate (MFP) to human beings or rats, a fraction of the drug appears in plasma that is bound to proteins, establishing a previously undetected compartment of nondiffusible fluoride. This article documents experiments performed in vitro, describing the binding of MFP to two plasma globulins: alpha2-macroglobulin and C3 (a beta-globulin). MFP binds irreversibly to these proteins through a stable bond. MFP binds to purified alpha2-macroglobulin or to C3 with a molar ratio MFP: protein close to unity. MFP binding reduces significantly the biological activity of these proteins, which share in common a macrocyclic 4-residue ring thiolactone (Cys-Gly-Glu-Glu). The binding site of MFP is as yet unknown. Protein-bound MFP appeared in the plasma of volunteers during the 5-7 hours following intake. Peak concentration of protein-bound MFP and maximal reduction of alpha2-macroglobulin activity was observed 2 hours after intake. Clearance of protein-bound MFP coincided with the return of alpha2-macroglobulin to basal levels.

Animals↗

PubMed1996

Protected bronchoalveolar lavage in the diagnosis of ventilator-associated pneumonia.

The aim of this study was to evaluate the diagnostic efficacy of protected bronchoalveolar lavage (PBAL) in ventilator-associated pneumonia (VAP), and to determine the effect of antibiotic therapy on its microbiological and cytological results. We prospectively studied 102 episodes of suspected VAP in 93 patients. Subsequent follow-up confirmed VAP in 35 of the 102 (34%) cases. In 55 of the 102 (55%) VAP was ruled out, and the diagnosis remained undetermined in 12 of the 102 (12%) episodes. In the VAP group, 30 of the 35 (86%) PBAL (> or = 10(4) colony-forming units (cfu)-mL-1) cultures were positive. In the non-VAP group, 5 of the 55 (9%) PBAL cultures were positive. A Giemsa stain of PBAL samples was performed in 32 of the 35 cases of VAP. Intracellular organisms (ICO) were found in 24 of the 32 (75%) cases. Seven of the other eight cases without evidence of ICO were already on antibiotics. In the non-VAP group, ICO were present in only 1 out of 55 (2%) cases. The mean ICO was significantly higher in the group who had not received antibiotics when compared with those patients previously treated for less than 48 h (p < or = 0.01) and those treated for more than 48 h (p = 0.009). The sensitivity of protected bronchoalveolar lavage quantitative cultures was 87% and the specificity 91%. The sensitivity of cytological analysis for intracellular organisms was 75% and the specificity 98%. According to our results, if the patient is already on antibiotics, the direct examination of protected bronchoalveolar lavage fluid is less reliable, although still helpful.

Anti-Bacterial Agents↗

PubMed1995

Efficacy, safety, and therapeutic relevance of transthoracic aspiration with ultrathin needle in nonventilated nosocomial pneumonia.

In order to determine the potential indications of transthoracic needle aspiration (TNA) using the ultrathin 25G needle for the diagnosis of nonopportunistic lung infections, we prospectively analyzed the diagnostic efficacy, safety, and therapeutic implications of its results in 97 patients with nonventilated nosocomial pneumonias (NVNP). The sensitivity of TNA was 60.9%. Specificity and positive predictive value (PPV) were 100%. Negative predictive value (NPV) was 34.1%. The complications in the studied cases were nil in 89 cases (91.8%), transient hemoptoic expectoration (< 10 ml) in five (5.2%), and self-limited partial pneumothorax in three (3.1%). No complications needing treatment were observed. On the basis of a positive TNA result, the initial antibiotic treatment was modified in 29 of 97 (29.9%) cases. In twelve of these, the empirical antibiotic regimen was demonstrated to be ineffective. We conclude that, using the 25G needle, TNA has a good diagnostic efficacy and is a safe procedure for the etiologic investigation of NVNP. A positive TNA result has significant therapeutic relevance, even in cases where broad-spectrum antibiotics are empirically prescribed.

Adolescent↗

PubMed1995

Risk factors for the development of Haemophilus influenzae pneumonia in hospitalized adults.

Potential risk factors for developing Haemophilus influenzae nosocomial pneumonia have not been sufficiently studied. We wanted to investigate the incidence and risk factors for the development of Haemophilus influenzae pneumonia in the hospital by means of a multivariate analysis. A total of 468 cases of nosocomial pneumonia were observed during the study period, 317 (68%) of which were aetiologically diagnosed by means of highly reliable methods, and H. influenzae was isolated in 57 of them. Fifty of the 57 episodes of H. influenzae pneumonia occurred in mechanically-ventilated patients. Underlying diseases were: medical in 12 cases, surgical in 15 cases, and traumatological in 22. Variables associated with Haemophilus influenzae nosocomial pneumonia in intubated patients after the univariate analysis were: "period between admission and pneumonia 2-7 days" and "no previous antibiotics". A multivariate analysis demonstrated that the variables "no previous antibiotics" and "coma on admission" were risk factors for H. influenzae pneumonia. In nonintubated patients, no risk factors were found for H. influenzae pneumonia compared with other nosocomial pneumonia. We conclude that H. influenzae was involved in 57 out of 317 (18%) of nosocomial pneumonia registered in our institution, and the majority of patients (50 out of 57) were mechanically-ventilated. In this particular subgroup, coma of the patient on admission to hospital and absence of antibiotic treatment prior to developing pneumonia constitute two definite risk factors for developing H. influenzae nosocomial pneumonia.

Adult↗

PubMed1992

Branhamella catarrhalis respiratory infections.

Branhamella catarrhalis is an aerobic Gram-negative diplococcus. It has been traditionally regarded as an oropharyngeal commensal and until recently was only identified as a pathogen in cases of bronchopulmonary infections. The aim of this study was to analyse the characteristics of the respiratory infections caused by B. catarrhalis and to know the antibiotic susceptibility of this microorganism. We retrospectively studied 32 lower respiratory tract infections, caused by B. catarrhalis (20 cases of bronchial infection and 12 cases of pneumonia), diagnosed between 1988-1989 in our hospital. All patients had an underlying disease; chronic obstructive pulmonary disease (COPD) and chronic heart disease being the most frequent. The aetiological diagnostic procedures were: sputum culture in 28 cases (15 in pure culture and 13 mixed), protected specimen brush (PSB) in three cases and transthoracic needle aspiration (TNA) in one case. Twenty B. catarrhalis isolates were penicillin and ampicillin-resistant, 11 in the pneumonia group and 9 in the bronchial infection group. All isolates were sensitive to amoxycillin-clavulanic acid and second generation cephalosporin. In our group four patients died. We conclude that B. catarrhalis is a not infrequent cause of respiratory infection, particularly in COPD patients, and that the high incidence of antibiotic resistance to penicillin and ampicillin should be taken into account before considering an empirical antibiotic treatment.

Aged↗

PubMed1990