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Biomedical subjects

M Riera

Publications and source records attributed to M Riera.

At least 19 recordsLinked to original sources

Transcriptome analysis of a rat PKD model: Importance of genes involved in extracellular matrix metabolism.

Transcriptome analysis of a rat polycystic kidney disease (PKD) model: importance of genes involved in extracellular matrix metabolism. PKD is a common genetic cause of chronic renal failure, and is characterized by the accumulation of fluid-filled cysts in the kidneys and other organs. Abnormalities in the expression of selected genes thought to be involved in cystogenesis have been described, but no systematic analysis of the global transcriptomal pattern has been reported. With this aim, a rat oligomicroarray was used to identify variations in gene expression in Han:Sprague-Dawley Cy/Cy rats, an animal model presenting a severe PKD phenotype. Some upregulated genes were validated using real-time polymerase chain reaction in Cy/Cy and Cy/+ rats. Among the 350 genes identified as being upregulated, we found about 30 genes involved in extracellular matrix metabolism. These genes encoded proteins or peptides that could be implicated into two different biological processes: molecules involved in fibrosis and proteins involved in adhesion to the extracellular matrix. In heterozygotes, some genes (glypican 3, fibronectin 1) were already upregulated in early stages of the disease. We conclude that differential regulation of genes linked to extracellular matrix metabolism may be one of the first events leading to tubule enlargement and subsequent cyst formation in PKD.

Animals↗

Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia.

The objective of this work was to study the role of mannose-binding lectin (MBL) and C-reactive protein (CRP) in pneumococcal pneumonia, to determine whether MBL acts as an acute-phase reactant and whether the severity of the disease correlates with MBL levels. The study comprised 100 patients with pneumococcal pneumonia. The pneumonia severity score was calculated and graded into a risk class of mortality (Fine scale). The MBL genotypes and the levels of MBL and CRP at the acute and recovery phases were determined. Fifty patients with the wild-type MBL genotype showed higher MBL levels in each phase (P < 0.001) and an increased risk to developing bacteraemia, odds ratio (OR) 2.74, 95% confidence interval (CI) 1.01-7.52) (P = 0.02), but this did not correlate with the pneumonia severity class. CRP levels in the acute phase, 79.53 mg/l [standard deviation (s.d.) 106.93], were higher in the subjects with positive blood cultures (P = 0.003), and remained higher [20.12 mg/l (s.d. 31.90)] in the group of patients with an underlying disease (P = 0.01). No correlation was observed between the levels of MBL and CRP in each phase, or with the pneumonia severity score. We cannot conclude that MBL acts uniformly as an acute-phase reactant in pneumococcal pneumonia. MBL levels do not correlate well with the severity of the pneumonia. The risk of developing bacteraemia could be enhanced in individuals with the wild-type MBL genotype.

Acute-Phase Reaction↗

Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics.

The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG(2)m and Fc(gamma)RIIa allotypes were determined. A history of drug abuse (P = 0.001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0.01), higher levels of HIV-1 viral load (P < 0.05), serum IgG (P < 0.01) and beta2-microglobulin (P < 0.01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG(2)m and Fc(gamma)RIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.

AIDS-Related Opportunistic Infections↗

The enhancement of endogenous cAMP with pituitary adenylate cyclase-activating polypeptide protects rat kidney against ischemia through the modulation of inflammatory response.

BACKGROUND: Cyclic nucleotide analogue administration improves ischemia-reperfusion damage in several organs. The neuropeptide pituitary adenylate cyclase-activating polypeptide, PACAP-38, is a potent stimulus to enhance cellular cAMP levels. This study tested the protective effect of enhancing endogenous cAMP levels by PACAP-38 in a model of warm renal ischemia. METHODS: Sprague-Dawley rats underwent 40 min of bilateral warm renal ischemia. PACAP-38 continuous infusion began either before ischemia or at 6 hr or 18 hr after ischemia. A mini-osmotic pump infused PACAP-38 throughout 7 days of follow-up. Groups were constructed with sham, ischemic control, and dibutyryl cAMP treated animals, and four PACAP-38 treatment groups, using 16 pmol/hr or 160 pmol/hr of the compound, or delaying its administration by 6 hr or 18 hr after ischemia. Renal function was assessed by means of serum creatinine levels on days 1, 2, 3, and 7 after ischemia. Conventional histology was performed on day 7. Renal myeloperoxidase (MPO) activity, infiltrating CD45+ cells, plasma and tissue cAMP, and serum IL-6 were measured. RESULTS: Continuous administration of the high concentration of PACAP-38 ameliorated renal function and morphologic abnormalities induced by warm ischemia. Treatment with dibutyryl cAMP produced morphologic protection but only partial functional effect on the ischemic kidney. A 6-hour delay in the administration of the compound after ischemia offered similar protective effect, whereas an 18-hr delay did not. The neuropeptide clearly increased circulating cAMP after ischemia but not cAMP in renal tissue. PACAP-38 increased circulating IL-6, and minimized renal inflammatory cell infiltration induced by ischemia-reperfusion injury, as evidenced by a reduction of MPO activity and the number of CD45+ cells in ischemic renal tissue. CONCLUSIONS: Enhancement of endogenous circulating cAMP with PACAP-38 modulates postischemic inflammatory response and strongly protects from ischemic acute renal failure, even when administration is delayed for 6 hr after injury.

Acute Kidney Injury↗

[Invassive infections caused by Group A streptococci: clinical characteristics and microbiological analyses in 31 cases].

BACKGROUND: In the last two decades an increase in the incidence of invassive Streptococcus pyogenes infections has been reported in several countries. The objective of this study was to determine the clinical features of these infections in our hospital. METHODS: Retrospective study (1995-1998) of patients admitted at Son Dureta Hospital, Palma de Mallorca, Spain, who had S. pyogenes recovered from blood, sterile fluids or soft tissues. Patients clinical records were reviewed and bacterial isolates characterized. RESULTS: A total of 31 patients with invassive infections caused by S. pyogenes were identified. The annual incidence rates (number of episodes/1,000 admissions) were: 0.13 (1995), 0.20 (1996), 0.27 (1997), and 0.23 (1998). The mean age of patients was 41 years. Seventy four percent of patients had some underlying disease, and the most relevant conditions included: diabetes mellitus (5), parenteral drug abuse (4), chronic alcoholism (3), chronic liver disease (3) and infection with the human immunodeficiency virus (3). The most common portal of entry was the skin (78%). The initial clinical presenting form was cellulitis (39%). Necrotizing fasciitis, septic shock, and streptococcal toxic shock syndrome (STSS) were observed in 9.6%, 12.9%, and 6.4% of patients, respectively. The mortality rate was 16.1%. The phenotypic characterization of S. pyogenes isolates indicated that most isolates were of mucoid type and identified 11 different M serotypes, M1 being the most common. CONCLUSIONS: A steady increase in the incidence of invassive infections caused by S. pyogenes was observed since 1995 to 1997 in our hospital. Patients with certain underlying conditions are more susceptible to acquire these infections. The worst outcome of these infections corresponded to elderly patients, those with septic shock or STSS. Most strains responsible for these infections were encapsulated and the M1 serotype predominated.

Adolescent↗

Maize protein kinase CK2: regulation and functionality of three beta regulatory subunits.

Biochemical and crystallographic data suggest that, in contrast with other organisms, the active maize protein kinase CK2 might be composed simply of a catalytic polypeptide (CK2alpha), thus lacking CK2beta regulatory subunits. To investigate the existence and functionality of CK2beta regulatory subunits in Zea mays, we have screened a maize cDNA library using different approaches and have isolated three full-length cDNAs encoding CK2beta regulatory subunits (CK2beta-1, CK2beta-2 and CK2beta-3) and a cDNA coding for a novel CK2alpha catalytic subunit, CK2alpha-3. The pattern of expression of all these alpha/beta subunits has been studied in different organs and developmental stages using specific probes for each isoform, and indicates that while CK2alpha subunits are constitutive, CK2beta subunits are expressed differentially during embryo development. The yeast two-hybrid system and pull-down assays have been used to study specific interactions between the different subunits. While CK2alpha subunits are unable to self-associate, preferential interactions between alpha/beta isoforms and beta/beta isoforms can be predicted. Furthermore, we show that maize CK2alpha/beta subunits assemble into a structural tetrameric complex which has very similar properties to those described in other organisms, and that expression of maize CK2beta subunits in yeast allows the rescue of the phenotypic defects associated to the lack of CK2 function, thus demonstrating the functionality of maize CK2beta regulatory subunits.

Amino Acid Sequence↗