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Biomedical subjects

F Blasi

Publications and source records attributed to F Blasi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with pneumonia. Mowgli Study Group.

The most common clinical signs, host responses and radiographic patterns were studied in 203 Italian children hospitalized for community-acquired pneumonia in order to clarify the role of clinical and radiological characteristics in the diagnosis of Mycoplasma pneumoniae and/or Chlamydia pneumoniae infections. Antibody measurements in paired sera and polymerase chain reaction on nasopharyngeal aspirates were used to establish the diagnoses of acute M. pneumoniae and C. pneumoniae infection, and the aetiologic data were correlated with the clinical, laboratory and radiographic data obtained on admission. No significant association was observed between evidence of M. pneumoniae and/or C. pneumoniae infection and periods of episode during the year, mean age of the study subjects, individual symptoms, physical findings or laboratory test results. Furthermore, no significant correlation was observed in relation to the radiological findings and M. pneumoniae and/or C. pneumoniae infection. This study shows that neither clinical findings nor laboratory parameters distinguished Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection in children with pneumonia. Radiological findings also have a limited capacity to differentiate aetiologic agents. The priorities for future research include the development of rapid, easily accessible and cost-effective diagnostic tests useful for each episode of pneumonia in children.

Acute Disease↗
PubMed2001

Independent regulation of initiation and maintenance phases of Hoxa3 expression in the vertebrate hindbrain involve auto- and cross-regulatory mechanisms.

During development of the vertebrate hindbrain, Hox genes play multiple roles in the segmental processes that regulate anteroposterior (AP) patterning. Paralogous Hox genes, such as Hoxa3, Hoxb3 and Hoxd3, generally have very similar patterns of expression, and gene targeting experiments have shown that members of paralogy group 3 can functionally compensate for each other. Hence, distinct functions for individual members of this family may primarily depend upon differences in their expression domains. The earliest domains of expression of the Hoxa3 and Hoxb3 genes in hindbrain rhombomeric (r) segments are transiently regulated by kreisler, a conserved Maf b-Zip protein, but the mechanisms that maintain expression in later stages are unknown. In this study, we have compared the segmental expression and regulation of Hoxa3 and Hoxb3 in mouse and chick embryos to investigate how they are controlled after initial activation. We found that the patterns of Hoxa3 and Hoxb3 expression in r5 and r6 in later stages during mouse and chick hindbrain development were differentially regulated. Hoxa3 expression was maintained in r5 and r6, while Hoxb3 was downregulated. Regulatory comparisons of cis-elements from the chick and mouse Hoxa3 locus in both transgenic mouse and chick embryos have identified a conserved enhancer that mediates the late phase of Hoxa3 expression through a conserved auto/cross-regulatory loop. This block of similarity is also present in the human and horn shark loci, and contains two bipartite Hox/Pbx-binding sites that are necessary for its in vivo activity in the hindbrain. These HOX/PBC sites are positioned near a conserved kreisler-binding site (KrA) that is involved in activating early expression in r5 and r6, but their activity is independent of kreisler. This work demonstrates that separate elements are involved in initiating and maintaining Hoxa3 expression during hindbrain segmentation, and that it is regulated in a manner different from Hoxb3 in later stages. Together, these findings add further strength to the emerging importance of positive auto- and cross-regulatory interactions between Hox genes as a general mechanism for maintaining their correct spatial patterns in the vertebrate nervous system.

Animals↗
PubMed2001

Atypical pathogens and asthma: can they influence the natural history of the disease?

The association between respiratory infections and asthma exacerbations was first observed in the early '70s. In particular, the role of viral upper respiratory tract infections has been evaluated both in pediatric and adult populations. More recently, evidence of Mycoplasma and Chlamydia pneumoniae involvement in asthma attacks has been reported. These pathogens are also involved in chronic asthma, and both in vitro and animal model studies indicate that atypical agents may play a role in the pathogenesis of the disease. Further research is required to determine whether specific antibiotic treatment may alter the natural history of asthma.

Adult↗
PubMed2001

Community-acquired pneumonia: role of atypical organisms.

M. pneumoniae infection occurs world-wide and is the most common cause of community-acquired pneumonia (CAP) in the 5 to 20 year-old age group. The most reliable diagnostic test is enzyme immunoassay that allows immunoglobulin (Ig)G and IgM titration and presents 92% sensitivity and 95% specificity on paired samples. Potentially active drugs are tetracyclines, macrolides, ketolides, lincosamides, streptogamines, chloramphenicol, and fluoroquinolones. The incidence of Legionella infection, in spite of its world-wide diffusion, is highly variable in different studies, ranging from 1% to 27% of CAP. The most likely mode of transmission is direct inhalation from Legionella-contaminated water-supply systems. Extrapulmonary manifestations are relatively common but nonspecific. However, some signs and symptoms may raise the suspicion of Legionella infection: a sputum Gram stain with a high number of neutrophils without any organism, hyponatremia, and diarrhea in a critically ill patient. Urinary radioimmunoassay (RIA) antigen detection is the method of choice for L. pneumophila serogroup 1. The best treatment regimen is a full three-week treatment with a macrolide (erythromycin, clarithromycin, azithromycin). An alternative treatment regimen may be the association of second generation fluoroquinolones with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella, so that their use as single agent may be hypothesised even if clinical data are still insufficient for a definitive indication. Chlamydia pneumoniae account for 6-20% of CAP depending on several factors such as setting of the studied population, age group examined, and diagnostic methods used. The current gold standard for serological diagnosis of acute infection is microimmunofluorescence testing. Tetracyclines and erythromycin show good in vitro activity and so far have been the most commonly employed drugs in the treatment of C. pneumoniae infection. New macrolides, ketolides, and new fluoroquinolones are other potentially effective drugs.

Chlamydophila Infections↗
PubMed2000

Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection.

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-microglobulin, and age-the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.

Adolescent↗
PubMed2000

Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy.

The importance of plasminogen activation, mediated by urokinase (uPA) and its receptor (uPAR), is well established in many physiologica and pathological processes, such as in cell migration and tumor-cell invasion. Recently, additional functions have been described for uPA and uPAR, particularly in cell adhesion and chemotaxis. The amounts of uPA and uPAR in various tumor types and in the plasma/serum samples of cancer patients have been shown to correlate with survival prognosis, indicating the relevance of these molecules in malignancy. We previously showed that in acute myeloid leukemia, a high level of plasma soluble uPAR (suPAR) at diagnosis correlates with poor response to chemotherapy. However, in this case, as in other cancers, the origin of suPAR is unknown. Therefore, we have now analyzed uPAR in cells, plasma, and urine of patients with acute leukemia (n = 35) at 0, 5, 14, 28, and 56 days after start of chemotherapy. In response to cytotoxic treatment, suPAR levels decreased rapidly, and the decreasing plasma suPAR (p-suPAR levels correlated highly with decreasing numbers of circulating tumor cells, suggesting that the elevated p-suPAR was produced by circulating tumor cells. Moreover, the p-suPAR level appeared to correlate with the amount of uPAR in tumor cell lysates at diagnosis. Our results also show for the first time that in lysates of circulating tumor cells, studied by immunoprecipitation and immunoblotting, uPAR was partly in fragmented form, whereas only full-length uPAR was found in normal leukocytes. We also detected fragmented suPAR in peripheral blood plasma, in urine, and especially in the plasma compartment of bone-marrow aspirates of acute myeloid leukemia patients, in a pattern differing considerably from that found in healthy individuals. Because proteolytic cleavage of uPAR induces a potent chemotactic response in vitro, it is possible that these fragments may play a role in the pathophysiology of acute leukemia.

Acute Disease↗
PubMed2000

Shedding and cleavage of the urokinase receptor (uPAR): identification and characterisation of uPAR fragments in vitro and in vivo.

Applying a novel, highly specific and sensitive immunoabsorption/Western blotting technique we have identified in vitro in conditioned cell culture medium and in vivo in human urine different soluble forms of the urokinase-type plasminogen activator receptor (uPAR/CD87). These include the uPAR fragment D2D3 and the never before identified domain 1 (D1) fragment. These forms correspond to fragments previously characterised as biologically active as inducers of chemotaxis and cell adhesion. We find that stimulation of U937 cells is associated with increased uPAR expression, cleavage of surface uPAR, and release of soluble fragments to the culture medium suggesting that monocytes are a source of the circulating and urinary soluble uPAR fragments found in vivo. Our study demonstrates that potentially biologically active uPAR fragments are produced in the human body, indicating a possible function in the regulation of not only proteolysis but also signal transduction related processes.

Humans↗
PubMed2000

Cooperative interactions between PBX, PREP, and HOX proteins modulate the activity of the alpha 2(V) collagen (COL5A2) promoter.

Cell type-specific expression of the human alpha2(V) collagen (COL5A2) gene depends on a cis-acting element that consists of two contiguous protein binding sites (FPA and FPB) located between nucleotides -149 and -95, relative to the transcription start site. The present study focused on the characterization of the FPB-bound complex. DNA binding assays and cell transfection experiments revealed that the bipartite core sequence of FPB (5'-ATCAATCA-3') binds the PBX1/2, PREP1, and HOXB1 proteins, and this in turn leads to promoter transactivation. In the presence of all three nuclear factors, cooperative interactions between recombinant PBX1 and PREP1 or PBX1 and HOXB1 result in binding of the heterodimers to FPB in vitro. Similarly, overexpression of different combinations of PBX1, PREP1, and HOXB1 transactivates FPB-driven transcription. In contrast to the composition of the FPB complex purified from COL5A2-positive cells, the FPB complex from COL5A2-negative cells contains PBX2 and PREP1 but lacks PBX1. However, PBX1 exogenously introduced into COL5A2-negative cells cannot stimulate FPB-driven transcription unless co-expressed with PREP1. Within the intrinsic limitations of the experimental model, our results indicate that combinatorial interactions among PBX and PREP or HOX proteins are involved in regulating tissue-specific production of collagen V.

Base Sequence↗
PubMed2000

cRel-TD kinase: a serine/threonine kinase binding in vivo and in vitro c-Rel and phosphorylating its transactivation domain.

The activity of transcription factors is often modulated by signal responsive protein kinases. Rel/NF-kappaB transcription factors are regulated by IkappaB inhibitors, the phosphorylation of which causes ubiquitination and degradation, resulting in nuclear translocation of NF-kappaB and activation of target genes. Here we report pulldown and immunoprecipitation experiments showing that a mammalian 66 kDa protein kinase binds murine c-Rel, both in vitro and in vivo. This kinase appears to have at least two binding sites on c-Rel, a proline-directed serine/ threonine substrate specificity similar to MAP kinases and to specifically phosphorylate the C-terminal domain of murine c-Rel at an ERK consensus site.

Animals↗
PubMed2000

Domain 1 of the urokinase receptor (uPAR) is required for uPAR-mediated cell binding to vitronectin.

In the present paper we have analyzed uPAR-mediated cellular binding to vitronectin using the murine erythroid progenitor cell line 32D. We show that expression of uPAR in 32D cells promotes cellular binding to vitronectin, but fails to support cell spreading. The strength of binding is correlated to the expression level of uPAR and is strongly stimulated by the presence of uPAR ligands. Using a truncated variant of uPAR lacking domain 1 and by antibody inhibition experiments, we demonstrate that domain 1 plays a crucial role in uPAR-mediated cellular binding. The failure of the mutant uPAR to promote cellular binding is paralleled by a strong reduction in the affinity for vitronectin in vitro.

Animals↗
PubMed2000

Direct interaction of two homeoproteins, homothorax and extradenticle, is essential for EXD nuclear localization and function.

The Drosophila Homothorax (HTH) and Extradenticle (EXD) are two homeoproteins required in a number of developmental processes. EXD can function as a cofactor to Hox proteins. Its nuclear localization is dependent on HTH. In this study we present evidence of in vivo physical interaction between HTH and EXD, mediated primarily through an evolutionarily conserved MH domain in HTH. This interaction is essential for the mutual stabilization of both proteins, for EXD nuclear localization, and for the cooperative DNA binding of the EXD-HTH heterodimer. Some in vivo functions require both EXD and HTH in the nucleus, suggesting that the EXD-HTH complex may function as a transcriptional regulator.

Amino Acid Sequence↗
PubMed2000

Application of a computerised method to measure static pressure volume curve in acute respiratory distress syndrome.

OBJECTIVE: To assess the safety and the bedside feasibility of a new computerised method to record the static pressure-volume curves (Pst/V) of the respiratory system. DESIGN: The Pst/V curves were recorded in 13 medical patients with the acute respiratory distress syndrome (ARDS). During the Pst/V curve tracing the following parameters were recorded: time required for the recording and the automatic analysis of the Pst/V curve and modifications in electrocardiograms, blood pressure, and arterial oxygen saturation (SaO(2)). SETTING: The study was performed in the intensive care unit of the University of Naples "Federico II". RESULTS: No statistically significant modifications in heart rate (HR, b min(-1)), blood pressure (BP, mmHg), and SaO(2) were observed between conditions at baseline (HR 97.2 +/- 17.7; BP 65.4 +/- 9.3; SaO(2) 93.6 +/- 2.0), during the recording (HR 99.8 +/- 19.5; BP 66.2 +/- 11.6; SaO(2) 93.7 +/- 2.4), and 2 min after the procedure (HR 98.2 +/- 17.8; BP 65.2 +/- 11.7; SaO(2) 93.7 +/- 1.9). The Pst/V curves were recorded in 8.38 +/- 1. 19 min and fully analysed in 2.69 +/- 0.85 min. Mean value of static compliance was 41.1 +/- 12.7 ml cmH(2)O(-1). A lower inflection point was found in ten patients (mean value 9.2 +/- 1.9 cmH(2)O). CONCLUSIONS: In ARDS patients, the present new computerised method gave valuable data to ordinary intensivists and was shown to be safe, easy, and fast.

APACHE↗
PubMed2000

Serological evidence of infection with Chlamydia pneumoniae is related to the severity of asthma.

There is evidence that infection with Chlamydia pneumoniae is associated with asthma of recent onset and that it can influence the severity of asthma. This has led to the suggestion that macrolide antibiotics may be useful in the treatment of asthma in subjects infected with C. pneumoniae. This study examined the association between immunoglobulin (Ig)G and IgA titres to C. pneumoniae and the severity of asthma. IgG and IgA antibodies to C. pneumoniae were measured in 619 subjects with asthma (18-60 yrs), using the microimmunofluoresence method. Subjects were asked about their use of asthma medicines, symptoms, previous hospitalization for asthma, smoking status and age of onset of asthma. In subjects with IgG titres of > or =1:64 and/or IgA titres > or =1:16 (n=212), spirometry was performed and peak expiratory flow rate (PEFR) and symptoms were recorded twice daily for 4 weeks on a diary card. The use of high dose inhaled steroids was associated with an increase of 74.1% in the titre of IgG antibodies (p=0.04) and an increase of 70.6% in the titre of IgA antibodies (p=0.0001) when compared with the use of low dose inhaled steroids. There was an inverse association between IgG antibodies and forced expiratory volume in one second (FEV1) as a percentage of predicted in those subjects with elevated IgG and/or IgA (p=0.04). In this group IgA antibodies were also associated with a higher daytime symptom score (p=0.04). Higher titres of antibodies to Chlamydia pneumoniae appears to be associated with markers of asthma severity. This raises the possibility that chronic infection with Chlamydia pneumoniae leads to an increase in the severity of asthma. Studies aimed at eradicating chronic infection with Chlamydia pneumoniae are necessary to determine whether or not this is the case.

Administration, Inhalation↗
PubMed2000

Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae in reactive airway disease, 71 children aged 2-14 yrs with an acute episode of wheezing and 80 age-matched healthy children were studied. Sera for the determination of specific antibody levels and nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae deoxyribonucleic acid were obtained on admission and after 4-6 weeks. All children with wheezing received a standard therapy with inhaled corticosteroids and bronchodilators for 5-7 days; when antibiotic was added on the basis of the judgement of the paediatrician in charge, clarithromycin 15 mg.kg body weight(-1).day(-1) for 10 days was used. Acute M. pneumoniae and C. pneumoniae infections were detected significantly more often in children with wheezing than in controls. In patients infected with one of the two pathogens, a history of recurrent wheezing was significantly more frequent than in those without either infection. During a 3-month follow-up period, among nonantibiotic-treated children, those with acute M. pneumoniae and/or C. pneumoniae infection showed a significantly higher recurrence of wheezing than those without acute M. pneumoniae and/or C. pneumoniae infection (p=0.03). These results highlight the apparently significant relationship of Mycoplasma pneumoniae and Chlamydia pneumoniae with wheezing in children, particularly in subjects with a history of recurrent episodes, and the possible improvement in the course of reactive airway disease within paediatric patients with acute Mycoplasma pneumoniae and/or Chlamydia pneumoniae infection.

Acute Disease↗
PubMed2000

Oct-1 specifically binds the UEF4 site of the human AP1-regulated urokinase enhancer.

The inducible urokinase enhancer contains three essential elements: a combined PEA3/AP1 and a downstream AP1 site, separated by a 74-bp DNA region called COM (cooperation mediator), that is required for the synergism between the three sites. The 5' half of COM (uCOM) forms four retarded complexes with HeLa or HepG2 nuclear proteins (UEF1-4). We now demonstrate that the UEF4 complex is the transcription factor Oct-1. Because of functional redundancy of the UEF sites, single mutations in UEF4 have no phenotype; we have changed UEF4 from a low to a high affinity binding site for Oct-1. In vitro, this mutation increases the DNA binding of Oct-1 and disturbs the binding of the Prep-Pbx complexes to the nearby UEF3 site. In vivo, this mutation reduces the basal transcriptional activity of the urokinase enhancer, while not affecting its phorbol ester inducibility. This is in keeping with the effect of the deletions of the COM region, which result in an increase in the basal level and, as a consequence, in the loss of 4beta-phorbol 12-myristate 13-acetate inducibility. Oct-1 therefore is not involved in the inducibility of the urokinase enhancer but only in determining its basal activity level.

Base Sequence↗
PubMed2000

Chlamydia pneumoniae serology: interlaboratory variation in microimmunofluorescence assay results.

The lack of standardization in chlamydia serology has made interpretation of published data difficult. This study was initiated to determine the extent of interlaboratory variation of microimmunofluorescence (MIF) test results for the serodiagnosis of Chlamydia pneumoniae infections. Identical panels of 22 sera were sent to 14 laboratories in eight countries for the determination of IgG and IgM antibodies by MIF. Although there was extensive variation in the numeric titer values, the overall percentage agreement with the reference standard titers from the University of Washington was 80%. For results by serodiagnostic category, the best agreement was for four-fold rise in IgG titers, while the lowest agreement was for negative or low IgG titers. Agreement for IgM titers was 50%-95%. Four laboratories failed to discern false-positive IgM titers possibly because of the presence of rheumatoid factor. Further studies are underway to determine the source of interlaboratory variation for the MIF test.

Antibodies, Bacterial↗