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Biomedical subjects

J Roig

Publications and source records attributed to J Roig.

At least 19 recordsLinked to original sources
PubMed2006

13--Antibiotic therapy of community-acquired pneumonia (CAP) caused by atypical agents.

Macrolides, fluoroquinolones, doxycycline, and ketolides show a good intrinsic activity against intracellular pathogens which are responsible for a variable percentage of community-acquired pneumonia (CAP). These therapeutic agents all seem effective in treating most cases of CAP caused by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella spp. Among quinolones, the more recent fluoroquinolones, such as gemifloxacin or moxifloxacin, generally show a better intrinsic activity than the older ones. Among macrolides, azithromycin, and clarithromycin show a better pharmacokinetic profile. Both of them are available in intravenous form. It is quite common for M. pneumoniae and C. pneumoniae to continue to be shed in respiratory secretions, weeks after an effective therapy. The clinical relevance of this finding is not clear since most of these patients have a good outcome. Azithromycin, due to its advantageous pharmacokinetic profile, seems the best option when antibiotic prophylaxis is considered in some epidemiological settings. It has been proved effective in closed M. pneumoniae outbreaks.

Anti-Bacterial Agents↗
PubMed2006

Time-dependent folding of immunological epitopes of the human chorionic gonadotropin beta-subunit.

We have explored the possibility to use 14 different monoclonal antibodies in order to follow the formation of the respective epitopes during the biosynthesis of hCG subunits and their association in JEG-3 choriocarcinoma cells using pulse (30s to 5 min)-chase (0-180 min) experiments. We found central cystine knot epitope structures (epitope beta1) to be formed immediately and simultaneously with epitopes on the protruding hCG-beta loops 1 and 3. We found also differences in the time-dependent folding of beta2 and beta4 epitopes, which are highly overlapping structures on the loops 1+3. These differences were reinforced by decreasing the temperature during the pulse-chase experiments to 25 degrees C. Moreover, we describe for the first time an intracellular intact hCG beta-subunit form that showed the transient expression of the hCG-beta-core fragment epitope beta11 in the course of the maturation of this subunit which casts new light on the presence of hCG-beta-core fragment in Down's syndrome, tumors and pregnancy.

Antibodies, Monoclonal↗
PubMed2006

Implications of COPD in patients admitted to the intensive care unit by community-acquired pneumonia.

The mortality rate of chronic obstructive pulmonary disease (COPD) patients with community-acquired pneumonia (CAP) is reported to be low. However, studies carried out to date have included <20% of critically ill patients. The current authors performed a secondary analysis of a prospective study evaluating 428 immunocompetent patients admitted to the intensive care unit (ICU) for severe CAP. In total, 176 COPD patients were compared with 252 non-COPD patients. In COPD patients, ICU mortality (odds ratio (OR) 1.58; 95% confidence interval (CI) 1.01-1.43) and mechanical ventilation (OR 2.78; 95% CI 1.63-4.74) rates were higher than in non-COPD patients. The ICU mortality was 39% for COPD patients initially intubated and 50% for those who failed noninvasive ventilation. The proportion of patients who were males, aged >/=70 yrs, smokers and who had chronic heart disease or Pseudomonas aeruginosa were higher in COPD patients. Inappropriate empirical antibiotic therapy was associated with higher mortality (OR 3.8; 95% CI 1.19-12.6). ICU mortality in COPD patients with adequate therapy was associated with bilateral pneumonia (OR 2.32; 95% CI 1.18-4.53) and shock (OR 3.53; 95% CI 1.31-9.71). In conclusion, chronic obstructive pulmonary disease patients hospitalised with community-acquired pneumonia in the intensive care unit had higher mortality and need of mechanical ventilation when compared with patients without chronic obstructive pulmonary disease.

Aged↗
PubMed2006

The pneumonia severity index predicts time to clinical stability in patients with community-acquired pneumonia.

SETTING: A total of 33 hospitals in 13 countries in North America, Europe, Africa, Asia and Latin America. OBJECTIVE: To investigate the relationship between the pneumonia severity index (PSI) and the time to clinical stability from intravenous to oral antibiotic therapy in hospitalized adult patients with community-acquired pneumonia (CAP). DESIGN: An international, retrospective, observational study of random adult patients meeting the definition of CAP between June 2001 and May 2004. RESULTS: The risk class (RC) according to the PSI was calculated for all patients. The criteria to define when a patient is clinically stable were evaluated daily during the first 7 days of hospitalization in all patients. The mean time to clinical stability for 254 patients in RC I was 4.2 days, for 233 patients in RC II it was 3.9 days, for 395 patients in RC III it was 4.6 days, for 644 patients in RC IV it was 5.0 days and for 296 patients in RC V it was 6.0 days. Significant positive correlations were observed between RC and time to clinical stability (P < 0.0001). CONCLUSION: The PSI is a tool that can be used to predict time to clinical stability (i.e., time to antimicrobial switch therapy) in hospitalized patients with CAP.

Anti-Bacterial Agents↗
PubMed2003

Membrane treatment by nanofiltration of exhausted vegetable tannin liquors from the leather industry.

A rational use of water in the leather industry is described by applying the criteria of "clean technologies" by means of membrane processes. A nanofiltration (NF) process was used for recovering tannins and water from exhausted baths and reusing them as tanning agents and washings. Results of experiments performed on laboratory and semi-industrial pilot scale plants, operating and fluid-dynamic conditions and mass balance of the NF process are reported and discussed. Chemical and physical analytical values measured on skins treated with the recovered solutions were very similar to those measured on control skins tanned with standard solutions. According to the obtained results, a process scheme is suggested. It permits both to recover water and to increase the tannin/non tannin (T/NT) ratio in the retentate solution, starting from exhausted tanning baths and by using a NF membrane purification/concentration. The final volume reduction factor of tested exhausted baths was 5.25, the increase of T/NT ratio was from 1.1 to 2.3 and the average permeate flux was 12.5l/m(2)h. Advantages are in terms of: reduction of environmental impact (up to 75% of COD reduction of the global effluent), simplification of cleaning-up processes of wastewaters, decrease of disposal costs, saving of chemicals and water.

Conservation of Natural Resources↗
PubMed2001

Cdc42-independent activation and translocation of the cytostatic p21-activated protein kinase gamma-PAK by sphingosine.

Autophosphorylation of p21-activated protein kinase gamma-PAK is stimulated at 10 microM sphingosine in vitro and is maximal at 100 microM. Sites autophosphorylated on gamma-PAK in response to sphingosine are identical to those obtained with Cdc42(GTP). Autophosphorylation is paralleled by stimulation of gamma-PAK activity as measured with peptide and protein substrates. In 3T3-L1 cells, sphingosine stimulates the autophosphorylation and activity of gamma-PAK associated with the membrane-containing particulate fraction by 2.8-fold, but does not stimulate the activity of the soluble enzyme. Thus, gamma-PAK is activatable via a Cdc42-independent mechanism, suggesting sphingosine has a role in gamma-PAK activation under conditions of cell stress.

3T3 Cells↗
PubMed2001

Cytostatic p21 G protein-activated protein kinase gamma-PAK.

The p21-activated protein kinase gamma-PAK, also known as PAK2, has very different properties from the other two highly conserved isoforms of the PAK family, alpha-PAK (PAK1) and beta-PAK (PAK3). gamma-PAK has cytostatic activity, as shown by inhibition of cleavage of early frog embryos following microinjection of gamma-PAK and by inhibition of growth when expressed in mammalian cells. gamma-PAK is activated in response to a variety of stresses including radiation- and chemically-induced DNA damage, hyperosmolarity, addition of sphingosine, serum starvation, and contact inhibition. Activation occurs through at least two signaling pathways, depending on the type of stress, one of which requires phosphoinositide 3-kinase and/or tyrosine kinase activity. During apoptosis gamma-PAK is cleaved by caspase 3 and activated and appears to have a role in the apoptotic response. gamma-PAK is present in the cytosol, associated with the membrane and in secretory granules. A wide variety of substrates have been identified for gamma-PAK. We propose gamma-PAK may be involved in coordinating the stress response, possibly in conjunction with other stress response proteins.

Animals↗
PubMed2000

Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.

A member of the p21-activated protein kinase (PAK) family, gamma-PAK has cytostatic properties and is activated by cellular stresses such as hyperosmolarity or DNA damage. We report herein that gamma-PAK is associated in vivo with the nonreceptor protein tyrosine kinase c-Abl. gamma-PAK phosphorylates c-Abl on sites located in the kinase domain, in a region that is implicated in protein-protein interactions and in subcellular localization. Activation of gamma-PAK in human embryonic kidney 293T cells by cotransfection with constitutively active Cdc42 induces activation of c-Abl, resulting in increased phosphotyrosine levels. Cotransfection of c-Abl and gamma-PAK elicits phosphorylation of gamma-PAK on tyrosine and down-regulation of gamma-PAK activity, promoting accumulation of inactive gamma-PAK. gamma-PAK is also phosphorylated in vitro by c-Abl. gamma-PAK activity is regulated by ubiquitination and proteolysis in vivo, as shown by immunoblotting with an anti-ubiquitin antibody in the presence of proteasome inhibitors. In summary, we describe a functional interaction between gamma-PAK and c-Abl in which gamma-PAK stimulates c-Abl tyrosine kinase activity and c-Abl phosphorylates and down-regulates gamma-PAK, suggesting the existence of a negative feedback loop between c-Abl and gamma-PAK.

Cell Line, Transformed↗
PubMed2000

p21-activated protein kinase gamma-PAK is translocated and activated in response to hyperosmolarity. Implication of Cdc42 and phosphoinositide 3-kinase in a two-step mechanism for gamma-PAK activation.

A member of the family of p21-activated protein kinases, gamma-PAK, has cytostatic properties and is activated during apoptosis and in response to DNA damage. To determine whether gamma-PAK is activated by other types of cell stress and to assess its mechanism of activation, the response of gamma-PAK to hyperosmotic stress was examined. In 3T3-L1 mouse fibroblasts, there are two pools of gamma-PAK: the majority of the protein kinase is soluble and has low specific activity, whereas gamma-PAK associated with the particulate fraction has significantly higher specific activity. Hyperosmolarity promotes translocation of gamma-PAK from the soluble to the particulate fraction; this parallels activation of the protein kinase. Activation but not translocation of gamma-PAK is wortmannin-sensitive, suggesting the involvement of a phosphoinositide 3-kinase-related activity. gamma-PAK translocation in response to hyperosmolarity parallels Cdc42 translocation to the particulate fraction in vivo and can be induced in vitro by guanosine 5'-3-O-(thio)triphosphate. Cotransfection of gamma-PAK with constitutively active Cdc42 induces gamma-PAK activation and translocation, whereas inactive Cdc42 inhibits both processes in response to hyperosmotic stress, suggesting that Cdc42 has a role in the translocation and activation of gamma-PAK. alpha-PAK is not activated in response to hyperosmolarity in 3T3-L1 cells. A two-step model of gamma-PAK activation is presented.

3T3 Cells↗
PubMed1999

p21-activated protein kinase gamma-PAK is activated by ionizing radiation and other DNA-damaging agents. Similarities and differences to alpha-PAK.

The p21-activated protein kinase gamma-PAK is activated 2-5-fold in response to ionizing radiation (IR) in 3T3-L1 fibroblasts and U937 leukemia cells. gamma-PAK is activated in a dose- and time-dependent manner. Doses from 1 to 100 Gy result in significant stimulation of activity at 30 min, whereas maximal stimulation is observed at 120 min after irradiation. UV (80 J/m(2)) and the DNA-damaging drugs cytosine beta-D-arabinofuranoside (AraC) and cis-platinum(II)diammine dichloride (cisplatin) also induce gamma-PAK activation. The activation of gamma-PAK in response to IR or AraC is dependent on tyrosine kinase and phosphoinositide 3-kinase activity, as demonstrated by use of the inhibitors genistein and wortmannin; in contrast activation of gamma-PAK by cisplatin and UV is not affected significantly by these inhibitors, suggesting that gamma-PAK can be activated by more than one pathway in response to different types of DNA damage. In contrast to gamma-PAK, alpha-PAK and JNK are activated only by cisplatin and UV in 3T3-L1 cells, suggesting differential regulation of the protein kinases. This is the first time that members of the Ste20/PAK family of protein kinases have been shown to be involved in the cellular response to IR and other DNA-damaging agents.

3T3 Cells↗
PubMed1999

Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial.

In 1989, we began a multicenter study to evaluate the potential benefit of preoperative chemotherapy with cisplatin, ifosfamide and mitomycin over surgery alone in CT-visible N2 non-small-cell lung cancer. We present here a 7-year assessment of this randomized trial. Sixty patients were randomized to receive either surgery alone or three cycles of mitomycin 6 mg/m2, ifosfamide 3 g/m2 and cisplatin 50 mg/m2, given intravenously on day 1 of each cycle at 3-week intervals and followed by surgery. All patients received thoracic irradiation after surgery. The resected tumors were evaluated for the presence of K-ras gene point mutations. Treatment arms were well-balanced in characteristics such as gender, age, histology, and tumor size. Mediastinoscopy and/or mediastinotomy (Chamberlain procedure) with a biopsy was performed in all patients with N2 stage detected by CT scan of the chest (83% of the patients in the preresectional chemotherapy arm and 63% of those in the surgery arm). In eight of the 25 patients (32%) who had mediastinoscopy in the preresectional chemotherapy arm, the initially positive mediastinal lymph nodes were downstaged. For the 30 patients who received preresectional chemotherapy, overall median survival was 22 months (95% CI, 13.4 30.6). Of the 30 patients who received surgery alone, overall median survival was 10 months (95% CI, 7.4-12.6; P = 0.005 by the log rank test). Updated survival data reveals a plateau in the preresectional chemotherapy group, and this still significant long-term survival benefit prompts us to hypothesize that even with short-term preresectional chemotherapy, the natural history of still resectable CT-visible N2 non-small cell lung cancer is favorably altered. The results of our study mirror the long-term survival recently reported in the MD Anderson randomized study.

Adult↗
PubMed1999

Inhaled antibiotic therapy in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa.

The aim of this study was to investigate the long-term effectiveness and safety of inhaled antibiotic treatment in non-cystic fibrosis patients with bronchiectasis and chronic infection by Pseudomonas aeruginosa, after standard endovenous and oral therapy for long-term control of the infection had failed. After completing a 2-week endovenous antibiotic treatment to stabilize respiratory status, 17 patients were randomly allocated to a 12-month treatment either with inhaled ceftazidime and tobramycin (group A) or a symptomatic treatment (group B). One patient from group A abandoned inhaled treatment because of bronchospasm and another from group B died before the end of the study. The remaining 15 patients, seven from group A and eight from group B, completed the study. Both groups had similar previous characteristics. The number of admissions and days of admission (mean +/- SEM) of group A [0.6 (1.5) and 13.1 (34.8)] were lower than those of group B [2.5 (2.1) and 57.9 (41.8)] (P < 0.05). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), PAO2 and PACO2 were similar in the two groups at the end of follow-up, showing a comparable decline in these parameters. There were no significant differences either in the use of oral antibiotics or in the frequency of emergence of antibiotic-resistant bacteria between groups. Microbiological studies suggested that several patients had different Pseudomonas aeruginosa strains. None of the patients presented impaired renal or auditory function at the end of the study. This study suggests that long-term inhaled antibiotic therapy may be safe and lessen disease severity in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection by Pseudomonas aeruginosa which do not respond satisfactorily to antibiotics administered via other routes.

Administration, Inhalation↗
PubMed1999

Multiple forms of protein kinase CK2 present in leukemic cells: in vitro study of its origin by proteolysis.

Human recombinant CK2 subunits were incubated for different times with the two main cytosolic proteases m-calpain and 20 S proteasome. Both, m-calpain in a calcium dependent manner and the 20 S proteasome, were able to degrade CK2 subunits in vitro. In both cases, CK2alpha' was more resistant to these proteases than CK2alpha. When these proteases were assayed on the reconstituted (alpha2beta2 holoenzyme), a 37 kDa alpha-band, analogous to that observed in AML extracts, was generated which was resistant to further degradation. No degradation was observed when the 26 S proteasome was assayed on free subunits. Studies with CK2alpha deletion mutants showed that m-calpain and the 20 S proteasome acted on the C-terminus end of CK2alpha. These results pointed to cytosolic proteases as agents involved in the control of the amount of free CK2 subunits within the cell, which becomes evident when CK2 is overexpressed as in AML cells.

Acute Disease↗