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F Lozano

Publications and source records attributed to F Lozano.

At least 19 recordsLinked to original sources
PubMed2006

Association of mannose-binding lectin gene polymorphisms with antiphospholipid syndrome, cardiovascular disease and chronic damage in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)-deficient genotypes with cardiovascular disease in a large series of patients with systemic lupus erythematosus (SLE). METHODS: A total of 114 patients diagnosed with SLE were included in the study. MBL polymorphisms were investigated by sequencing-based DNA typing of the promoter and exon 1 of the MBL2 gene. The genotypes 0/0, 0/XA and XA/XA were considered as MBL-low genotypes. RESULTS: A higher prevalence of cardiovascular disease was observed in patients carrying MBL-low genotypes compared with those carrying MBL-high genotypes [30 vs 9%, P = 0.012, odds ratio (OR) 4.54, 95% confidence interval (CI) 1.20-16.46]. Patients with MBL-low genotypes also presented higher mean values for total cholesterol (228.6 vs 202.3 mg/dl, P = 0.017) and low-density lipoprotein (LDL) cholesterol (139.9 vs 121.9 mg/dl, P = 0.045), a higher frequency of chronic renal failure (30 vs 4%, P = 0.001), vasculitis (30 vs 11%, P = 0.043), heart valve lesions (71 vs 32%, P = 0.026), cardiac valve dysfunction (57 vs 7%, P = 0.0004) and associated APS (39 vs 12%, P = 0.005), a higher mean Systemic Lupus International Collaborating Clinics score (2.09 vs 1.26, P = 0.029) and a lower prevalence of low C4 levels (43 vs 71%, P = 0.015). Multivariate analysis of genetic, clinical and immunological variables showed that only antiphospholipid syndrome (APS) was independently associated with cardiovascular events (P = 0.001). CONCLUSION: Although the prevalence of cardiovascular disease in our SLE patients carrying MBL-deficient genotypes was 3.3 times higher than in patients with non-deficient genotypes, only APS was independently associated with cardiovascular events. This suggests that the higher frequency of thrombotic events in SLE patients carrying MBL-deficient genotypes might be related to coexisting APS.

Adolescent↗
PubMed2006

Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus-coinfected patients.

Insulin resistance (IR) is a common condition in chronic hepatitis C. Recent studies have reported that IR is associated with liver fibrosis progression in these patients. However, there is no information available on this issue in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. For these reasons, we investigate the relationship between IR and liver fibrosis in patients with HIV and HCV infections. This was a cross-sectional study where patients from an Infectious Diseases Unit with HIV/HCV coinfection who underwent a liver biopsy, with available frozen sera samples at the time of biopsy and a known or estimated date of infection were included. IR was determined by the homeostasis model assessment (HOMA-IR) method. The relationship between histological findings and several variables, including HOMA-IR values, was examined. Seventy-nine patients fulfilled the inclusion criteria. Age at HCV infection >21 years was the only variable independently associated with advanced liver fibrosis (stages F3 and F4) [adjusted odds ratio (AOR) 4.15; 95% confidence interval (CI) 1.5-11.3]. The variables associated with a fibrosis progression rate above the median were age at HCV infection >21 years (AOR 6.41; 95% CI 2.16-27.96) and previous exposure to nevirapine (AOR 8.9; 95% CI 2.01-39.36). There was no association between HOMA-IR values and the presence of advanced fibrosis or a faster fibrosis progression. Thus IR is not associated with liver damage or fibrosis progression in HIV/HCV-coinfected individuals.

Adult↗
PubMed2005

Relationship between osteopenia, free testosterone, and vitamin D metabolite levels in HIV-infected patients with and without highly active antiretroviral therapy.

The prevalence of osteopenia in HIV-infected patients is high. However, the mechanisms implicated in bone mass loss in HIV infection are unclear. Because of this, we analyzed serum free testosterone and vitamin D3 hydroxylated metabolites in HIV-infected patients, with and without antiretroviral treatment, and the relation between them and osteopenia. Seventy-four HIV-infected patients were selected because they had frozen sera available at a date close to a DEXA evaluation. Free testosterone, 25(OH)D3, and 1,25(OH)2D3 were determined in frozen serum. There were no differences in free testosterone, 25(OH)D3, and 1,25(OH)2D3 levels between patients with and without osteopenia. 25(OH)D3 levels in naive and HAART-treated patients were 26.2 (10.3-32.8) and 33.1 (20.6-46.8) ng/ml, respectively (p = 0.04). 1,25(OH)2D3 levels in naive and HAART treated patients were 60.3 (49.2-80.8) and 85.5 (68-111.6) pmol/liter (p = 0.01). Free testosterone levels in 9 naive men and in 50 HAART-treated men were 42.6 (24.1-67.3) and 69.2 (47.5-112.1) pmol/liter, respectively (p = 0.04). In conclusion, HIV-infected patients with and without osteopenia showed similar levels of vitamin D metabolites and free testosterone. However, antiretroviral drug-naive patients showed lower serum levels of vitamin D metabolites and free testosterone than HAART-treated patients.

Adult↗
PubMed2005

Novel MASP2 variants detected among North African and Sub-Saharan individuals.

The lectin pathway of the complement system is activated when mannan-binding lectin (MBL) in complex with MBL-associated serine protease 2 (MASP-2) binds to carbohydrate structures on microorganisms. Structural gene mutations and promoter polymorphisms in the MBL2 gene responsible for low-MBL serum levels are present in all human populations and associate with increased risk of infection. Recently, investigations on Danes revealed the existence of a mutation on the MASP2 gene, which introduces an amino acid substitution in the CUB1 domain (Asp105Gly; numbering refers to the mature protein), and is associated with reduction in the level of MASP-2 in serum. Here, we present the results of a sequence-based typing analysis of the MBL2 and MASP2 gene polymorphisms in a group of 65 Africans (50 North Africans and 15 Sub-Saharan) and of 104 Spaniards. The analysis identified three novel exon 3 MASP2 variants introducing amino acid substitutions at positions 84 (Arg-->Gln), 103 (Arg-->Cys) and 111 (Pro-->Leu) in the CUB1 domain. None of these variants were identified in Spaniards. The Arg84Gln was detected in four of the 15 Sub-Saharans. The Arg103Cys and Pro111Leu variants were detected only among North Africans (two and four individuals, respectively). The Asp105Gly variant was similarly represented among Spaniards and North Africans (three and two individuals, respectively), which appears to be a lower frequency than that reported for Danes (5.5%). As reported for MBL2, the marked geographic distribution of the new MASP2 variants may represent an evolutionary adaptation to different environments.

Africa South of the Sahara↗
PubMed2004

Biochemical characterization of recombinant and circulating human Spalpha.

Human Spalpha is a soluble protein expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), for which little functional and structural information is available. It belongs to the group B of the scavenger receptor cysteine-rich superfamily (SRCR-SF) that includes the lymphocyte surface receptors CD5 and CD6 among others. Spalpha is able to bind to different cells of the immune system (monocytes and lymphocytes), which suggests that it may play an important role in the regulation of this system. To study Spalpha, an episomal mammalian expression system (pCEP-Pu/HEK 293-EBNA) was used to produce a recombinant form (rSpalpha) that was utilized for biochemical studies and for the generation of specific hybridomas. Four monoclonal antibodies were selected for their reactivity against rSpalpha by Western blot, immunoprecipitation, and enzyme-linked immunosorbent assays. The monoclonal antibodies recognized three different epitopes on Spalpha. The monoclonal antibodies revealed the existence of two Spalpha isoforms of 38 and 40 kDa, resulting from different sialic acid content. They also showed that Spalpha is a relatively abundant serum protein (60 micro g/ml) that mostly circulates in association with other serum proteins. Accordingly, rSpalpha allowed affinity chromatography isolation of polyclonal and monoclonal immunoglobulin M (IgM). These data indicate that Spalpha is a circulating protein that may play a role in the homeostasis of IgM antibodies.

Antibodies, Monoclonal↗
PubMed2003

Impaired recovery of CD4+ cell counts following highly active antiretroviral therapy in drug-naïve patients coinfected with human immunodeficiency virus and hepatitis C virus.

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is highly prevalent in southern Europe. However, there are few and contradictory data about the effect of HCV carriage on the response to highly active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T cells following HAART among antiretroviral-naïve patients seropositive for HIV with and without HCV coinfection was investigated. Two hundred one HIV-infected patients without previous exposure to antiretroviral drugs were included in the study. HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/ microl was longer in the HCV-positive group ( P<0.001). In a Cox model, HCV infection and lack of persistent HIV viremia (defined as <200 copies/ml) were associated with the time to recover 200 CD4+ cells/ microl. The mean increase in CD4+ cell counts was lower in the HCV-positive group during the first year of therapy. HIV/HCV-coinfected patients naïve for antiretroviral therapy show a delayed recovery of CD4+ cell counts after starting HAART.

Adult↗
PubMed2003

Characterization of a new HLA-C allele: Cw*1606.

HLA-Cw*16 is a relatively common HLA-C specificity among Caucasoids, with Cw*1601 being the most frequent allele. We report herein the identification by sequence-based typing of a new HLA-Cw*16 allele in a Spanish Caucasoid blood donor. The novel allele, designated Cw*1606, differs from Cw*1601 by two nucleotide changes at positions 361 (T to A) and 368 (A to C) in exon 3, which leads to two amino acid changes from Trp (TGG) to Arg (AGG) and from Tyr (TAT) to Ser (TCT) at codons 97 and 99 in the alpha2 domain, respectively. Sequence comparisons suggest that the new HLA-Cw*1606 variant could have arisen from an intralocus gene conversion event.

Alleles↗
PubMed2003

HLA-B*5130, a new HLA-B allele carrying a rare nucleotide substitution in exon 4.

We report herein the identification of a new HLA-B*51 allele in a Spanish Caucasoid organ donor. The novel allele, designated B*5130, differs from B*51011 by one nucleotide change at position 787 (A to G) in exon 4, leading to an amino acid change from Arg (AGA) to Gly (GGA) at codon 239 in the alpha3 domain. This substitution is present in most classical and nonclassical HLA class I loci (A, C, E, and G) but not in any of the HLA-B alleles reported so far, except for B*7301. Although the frequency of the new variant seems to be low, its existence makes mandatory the analysis of exon 4 before assigning a B*5101 type.

Alleles↗
PubMed2002

Impact of highly active antiretroviral therapy on fever of unknown origin in HIV-infected patients.

In order to assess the impact of highly active antiretroviral therapy (HAART) on the frequency and etiology of fever of unknown origin in HIV-infected patients, a retrospective study was performed on cases of fever of unknown origin observed from January 1997 to December 1999 in seven hospitals in five cities in Andalusia, Spain. During the period specified, a total of 4,858 HIV-infected patients receiving HAART and 2,787 HIV-infected individuals not receiving HAART were studied. The frequency of fever of unknown origin was 0.6% in patients receiving HAART and 3% in non-HAART patients (P=0.001). Human immunodeficiency virus infection was the only cause of fever found more frequently in the non-HAART patient group (P=0.07). The study findings suggest that the use of HAART has reduced the frequency of fever of unknown origin in HIV-infected patients, but the etiology of the condition remains mostly unchanged.

Adult↗
PubMed2001

Role of two conserved cytoplasmic threonine residues (T410 and T412) in CD5 signaling.

CD5 is a transmembrane coreceptor that modulates activation and differentiation signals mediated by the Ag-specific receptor present on both T and B1a lymphocytes. CD5 lacks intrinsic catalytic activity, and its immunomodulatory properties result from intracellular interactions mediated by the CD5 cytoplasmic tail. The nature of these interactions is currently a matter of investigation. Here, we present a selective mutagenesis analysis of two conserved threonine residues (T410 and T412) located at the membrane-proximal cytoplasmic region of CD5. These residues are contained within consensus phosphorylation motifs for protein kinase C and are shown here to be critical for in vivo protein kinase C-mediated phosphorylation of CD5. Functional studies revealed that the integrity of T410 and T412 is also critical for CD5-mediated phosphatidylcholine-specific phospholipase C (PC-PLC) activation and phorbol ester-mediated inhibition of Ab-induced internalization of CD5. These results strongly argue in favor of a role for T410 and T412 in the signaling mediated by CD5.

Amino Acid Substitution↗
PubMed2001

Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases.

The human CD5 lymphocyte cell surface co-receptor modulates activation and differentiation responses mediated by the antigen-specific receptor of T and B cells. CD5 is phosphorylated following lymphocyte activation; however, the exact sites and kinases involved are yet to be determined. Jurkat T cell transfectants expressing tyrosine-mutated CD5 molecules have been used to show that residues Y429 and Y463 are targeted in vivo by protein tyrosine kinases following cell stimulation with anti-CD3 mAb or pervanadate. This is in agreement with data from direct in vitro kinase assays using purified recombinant Lck and Fyn protein tyrosine kinases. The analysis of Lck- and CD3-deficient Jurkat cells shows that tyrosine phosphorylation of CD5 requires Lck activity. We propose that T cell activation mediates CD5 tyrosine phosphorylation at residues Y429 and Y463 mainly through the activation of Lck.

Amino Acid Substitution↗
PubMed2001

Identification of a novel single-nucleotide polymorphism (Val554Ile) and definition of eight common alleles for human IL4RA exon 11.

The interleukin (IL)-4 receptor alpha chain gene (IL4RA) is a polymorphic gene which is reportedly involved in the development of atopy. Of the 14 single-nucleotide polymorphisms (SNP) reported to date in the coding region of IL4RA, 11 are positioned to exon 11. This big exon encodes more than two thirds of the mature protein, including most of the cytoplasmic region. Here we report the identification of a new IL4RA SNP at the first nucleotide of codon 554 (GTA --> ATA) in exon 11, leading to an amino acid substitution from Val to Ile (V554I). Furthermore, we present complete nucleotide sequence data for eight common alleles resulting from combinations of 9 out of the 12 SNP at IL4RA exon 11. Homo- or heterozygous combinations of these eight alleles accounted for all the IL4RA exon 11 genotypes found in Caucasian individuals from our geographical area.

Alleles↗
PubMed2001

Identification of a new HLA-DRB1 allele (DRB1*0318) in three members of a Caucasian Spanish family.

This communication reports the identification of a new allele HLA-DRB1*03 in three members of a Caucasian Spanish family. The new allele has been officially named HLA-DRB1*0318 by the World Health Organization Nomenclature Committee. The exon 2 sequence of this new allele is identical to that of DRB1*03011 except for the first nucleotide of codon 45. The nucleotide change (C replacing G) leads to the amino acid substitution of glycine to arginine (GGG-->CGG) at position 45. This position of the beta1 domain shows very little polymorphism among DRB1* alleles (nucleotide changes at this position have only been reported for DRB1*1436 and DRB1*0105) and locates in the vicinity of the highly polymorphic position 47, which is a constituent of the groove's pocket interacting with the amino acid position 7 of the antigen peptide. The familial study showed that the new allele was maternally transmitted into the HLA-A*3002, -B*1801, -Cw*0501, -DRB1*0318, -DRB3*0202, -DQB1*0201 haplotype. Interestingly, the two siblings of the family, which were HLA identical and suffered of insulin-dependent diabetes mellitus (IDDM), were carriers of the two HLA haplotypes (DRB1*03/DQB1*0201 and DRB1*04/DQB1*0302) reported as susceptibility markers to IDDM in Caucasians.

Alleles↗
PubMed2001

Intravenous immune globulin effects on serum-soluble CD5 levels in atopic dermatitis.

BACKGROUND: Intravenous immune globulin (IVIG) therapy has been tried in the treatment of atopic dermatitis. Recently, the presence of serum-soluble CD5 (ssCD5) in atopic dermatitis was reported. OBJECTIVE: IVIG effects on ssCD5 levels in atopic dermatitis were examined and the correlation of ssCD5 level changes with clinical and laboratory parameters were investigated. METHODS: IVIG therapy was tried on 40 atopic dermatitis and 17 recurrent spontaneous abortion patients. Five atopic dermatitis patients received normal saline as a placebo control group. The clinical and laboratory parameters were evaluated on day 0, 1, 7 and 21 after administering the IVIG therapy. RESULTS: With IVIG therapy, in atopic dermatitis, the ssCD5 level was 5.5 +/- 6.2 ng/mL before infusion (day 0), 15.2 +/- 12.1 ng/mL on day 1, 13.8 +/- 14.1 ng/mL on day 7, and 3.9 +/- 4.1 ng/mL on day 21. The clinical severity score was 350.5 +/- 120.3 on day 0, 420.4 +/- 174.8 on day 1, 250.0 +/- 121.2 on day 7, and 115.5 +/- 53.9 on day 21. White blood cell (WBC) counts and serum IgE levels showed a gradual decrease with IVIG infusions. Blood eosinophil fractions were 5.3 +/- 2.8% on day 0, 8.6 +/- 5.2% on day 1, 7.3 +/- 3.7% on day 7, and 6.8 +/- 4.0% on day 21. Changes in the total eosinophil count were insignificantly parallel with those of blood eosinophil fractions CONCLUSION: In atopic dermatitis, IVIG therapy increased the ssCD5 levels. Further studies concerning the exact role of ssCD5 are needed.

CD5 Antigens↗
PubMed2001

High circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome.

OBJECTIVE: To determine the existence of circulating levels of soluble scavenger receptors (sCD5 and sCD6) in patients with primary Sjögren's syndrome (SS), and to analyse the correlation with clinical and immunological features of SS. METHODS: Ninety consecutive patients with primary SS were studied. All patients fulfilled four or more of the European diagnostic criteria for SS. sCD5 and sCD6 levels were determined using a specific enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. RESULTS: Detectable levels of sCD5 were found in 39 (43%) SS patients. The mean+/-standard error values of sCD5 were 3.5+/-0.5 ng/ml for patients with SS and 1.9+/-0.1 ng/ml for healthy blood donors (P<0.001). We found higher levels of sCD5 in patients with hypocomplementaemia (6.5 vs 3.5 ng/ml, P=0.03) and cryoglobulinaemia (6.9 vs 2.6 ng/ml, P=0.001). On the other hand, detectable levels of sCD6 were found in 60 (67%) SS patients. The mean+/-standard error values of sCD6 were 25.5+/-7.8 ng/ml in SS patients and 5.27+/-1.40 ng/ml in healthy blood donors (P=0.01). When the sCD6 levels were compared according to the presence or absence of immunological features, patients with cryoglobulinaemia showed higher levels of circulating sCD6 (77.3 vs 17 ng/ml, P=0.01) than those without cryoglobulinaemia. CONCLUSION: Patients with primary SS showed higher levels of circulating sCD5 and sCD6 when compared with controls. Moreover, the existence of some immunological features (hypocomplementaemia and cryoglobulinaemia) was associated with high levels of both soluble scavenger receptors. These facts may reflect an enhanced lymphocytic activation in patients with primary SS.

Adult↗
PubMed2001

Ruptured aneurysm of the deep femoral artery. Case report and historical review.

The exceptional characteristics of the case are put forward and commented on. The patient was a 96-year-old man with an arteriosclerotic aneurysm of the deep femoral artery, which became urgently apparent on bursting. The surgical resolution was simple and satisfactory. Later investigation showed that the aneurysm was unilateral and only in the deep femoral artery. Deep femoral artery continues to be an exceptional location of true arteriosclerotic aneurysms, above all when they arise in an isolated fashion. However, in recent years the available information has changed two substantial aspects: 1) these peripheral aneurysms have the greatest risk of rupture, and 2) on many occasions it is possible, when the superficial femoral artery is permeable, to give simple and satisfactory treatment (exclusion of the aneurysms without revascularization).

Aged↗