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Biomedical subjects

C Lahoz

Publications and source records attributed to C Lahoz.

At least 19 recordsLinked to original sources

Genetic restrictions in olive pollen allergy.

BACKGROUND: The major antigen of olive tree pollen, Ole e 1, produces an IgE response restricted by DQ2. OBJECTIVE: Our purpose was to further analyze the genetic restrictions associated with IgE and IgG antibodies against Ole e 1 and IgE against the recently described antigen Ole e 3. METHODS: Twenty-two nuclear olive pollen-allergic families (n = 88) were selected. DRB1 and DQB1, TCR-Valpha 8.1, the high-affinity receptor of IgE (FcepsilonRI-beta) Rsa I exon 7 and intron 2 and TNF-beta (LTalpha-Nco I) polymorphisms were determined by PCR and analyzed for association with allergic traits by the multiallelic transmission disequilibrium test. RESULTS: Significant associations were found among HLA-DQB1*0201 (n = 29) and high levels of IgG (P =.023) and IgE (P =.0136) antibodies to Ole e 1 and with IgE specific to Ole e 3 (P =.0368). DRB1*0701 was associated with high levels of total serum IgE (P =.04) and IgG against Ole e 1 (P =.025). The FcepsilonRI-beta Rsa I exon 7, allele 1 (n = 39), was associated with high levels of total serum IgE (P =. 01), IgE antibodies against Olea europaea extract (P =.004), and specific antibodies to Ole e 1, IgG (P =.04), and IgE (P =.006). The FcepsilonRI-beta Rsa I intron 2, allele 2 (n = 33), was associated with IgE antibodies to O europaea extract (P =.003) and specific antibodies to Ole e 1, IgG (P =.025), and IgE (P =.05). CONCLUSIONS: We found a new association between IgE antibody response to Ole e 3 and DQB1*0201 and verified the previously reported association between Ole e 1-specific response and DQB1*0201. Also, the association between FcepsilonRI-beta and IgE antibodies against Ole e 1 was demonstrated.

Adolescent

Interaction between galectin-3 and FcgammaRII induces down-regulation of IL-5 gene: implication of the promoter sequence IL-5REIII.

Our previous work demonstrated the capacity of galectin-3 (a beta-galactoside binding animal lectin) to inhibit IL-5 gene expression in different cell types, but the interaction of lectin with the cells and the pathways for the inhibition process are unknown. One of the purposes of this work was to study the cellular ligand for galectin-3. We have demonstrated that galectin-3 can bind to the low affinity IgG receptor (FcgammaRII or CD32) by using different experimental approaches, such as flow cytometry, fusion protein GST technology, and with a model of FcgammaRII-deficient mice. To further analyze the interaction between FcgammaRII and galectin-3, and its implication in IL-5 gene down-regulation we used FcgammaRII-deficient mice. When PBMC from these mice were incubated with galectin-3, the expression of the IL-5 gene was unchanged. However, when PBMC from wild type mice and FcgammaRIII-deficient mice were incubated with galectin-3, IL-5 gene expression was down-regulated. Finally, we studied the implication of the negative regulatory sequence in the IL-5 gene promoter. In the presence of galectin-3, a DNA-protein complex was formed with the IL-5REIII region. This complex was not observed when unrelated oligonucleotide was used. So, galectin-3 induces a pathway, which activates a transcription factor that binds to IL-5REIII. This interaction is capable of inhibiting IL-5 gene transcription.

Animals

Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles: The Framingham Offspring Study.

Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the -514T allele was due to an increase in the HDL(2)-C subfraction, and this association was stronger in women compared with men (P=0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C-514T polymorphism contributed significantly to the variability of HDL particle size in men and women (P<0.04). Thus, our results show that the C-514T polymorphism in the hepatic lipase gene is associated with significant variations in the lipoprotein profile in men and women.

Adult

Interferon beta-1b treatment modulates TNFalpha and IFNgamma spontaneous gene expression in MS.

BACKGROUND: Interferon beta (IFNbeta) lessens the overall frequency of acute attacks in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFNbeta may act by decreasing the synthesis of inflammatory cytokines. OBJECTIVES: To determine whether IFNbeta-1b treatment had an initial and sustained effect on the in vivo synthesis and secretion of tumor necrosis factor alpha (TNFalpha) and IFNgamma. METHODS: A highly sensitive reverse-transcriptase PCR technique was used to measure baseline levels of mRNA in freshly isolated cells from patients before therapy and at 3, 6, and 12 months of treatment. Also, protein concentration was measured in serum and in culture supernatants from mitogen-stimulated cells. The authors studied 16 patients, of whom 11 did not have clinical exacerbations, whereas 5 had one clinical relapse each during the study. RESULTS: Mean values of TNFalpha mRNA levels in the 11 stable patients decreased significantly at 3 and 6 months of treatment in comparison with initial data. After 6 months of therapy, IFNbeta-1b downmodulated TNFalpha transcripts in the 5 patients who experienced relapse. In this group of patients, TNFalpha levels rose sharply to reach pretreated values at 1 year of IFNbeta-1b treatment. At the beginning of therapy, 6 patients had high concentrations of serum TNFalpha, which decreased to normal values following IFNbeta-1b therapy. IFNgamma mRNA expression also diminished after 6 and 12 months of IFNbeta-1b therapy in the group of stable patients, whereas nonrelevant variations were observed in patients who had one relapse. Initially, patients' peripheral mononuclear cells secreted diminished amounts of TNFalpha and IFNgamma on PHA + PMA mitogen stimulation in comparison with normal control subjects. After 1 year of therapy, IFNbeta-1b restored the normal production of TNFalpha, whereas therapy did not restore IFNgamma secretion to control values. CONCLUSION: IFNbeta-1b decreases the spontaneous expression of two proinflammatory cytokines.

Adult

[Diets enriched with monounsaturated fatty acids and omega-3 polyunsaturated fatty acids decrease blood pressure without changing the plasma insulin concentration in healthy subjects].

BACKGROUND: Plasma glucose, insulin and blood pressure are wellknown cardiovascular risk factors, which may be influence by dietary factors. The aim of the study was to investigate whether changes in dietary fatty acids could modify plasma concentration of glucose, insulin and mean blood pressure (MBP). SUBJECTS AND METHODS: Forty two subjects (18 women and 24 men) were placed in four consecutive five week diet periods. Energy intake from proteins, carbohydrates and fats was constant during the study and there was only changes on fatty acids composition. First period was enriched on saturated fatty acids (SFA), second period on monounsaturated fatty acids (MUFA) and third and fourth periods were enriched on polyunsaturated fatty acids (PUFA). Fourth period was also enriched on PUFA n-3. RESULTS: No significant changes were found on glucose and insulin plasma concentration. However, a significant effect was detected on MBP on total population (p < 0.0001) and by gender. MUFA and PUFA n-3 enriched diet decreased significantly MBP compared to SFA enriched diet AGS (85.7, SD 9.1, 87.3, SD 8.7 y 90.3, SD 8.8 mmHg, respectively). In addition, a weak (r = 0.28) but significant (p = 0.002) correlation was found between MBP and plasma insulin. CONCLUSIONS: Diets enriched on MUFA fatty acids and n-3 fatty acids decrease significantly MBP without modifying glucose and insulin plasma concentration.

Analysis of Variance

Prenatal diagnosis on fetal cells obtained from maternal peripheral blood: report of 66 cases.

The potential use of fetal cells circulating in maternal blood for a non-invasive prenatal diagnosis has been widely described. Several authors have developed different methods for the enrichment of fetal cells from maternal peripheral blood. The aim of this study was to make a practical valuation of this new prenatal diagnosis technique, using those methods described as efficient and easy to carry out in a prenatal diagnosis unit. These methods consist of the double-density gradient and the positive selection by magnetic activated cell sorting (MACS) of the fetal erythroblasts, and the posterior study of the cells applying the FISH interphasic technique. Once the technique was ready, we obtained results from the study of 66 venous blood samples from women coming for prenatal diagnosis. Using a specific staining for fetal haemoglobin, fetal cells were identified in 63 cases. Fetal sex was well determined in 56 cases, 23 females and 33 males; in 7 cases the sex determination failed. All the aneuploidies found in a previous prenatal diagnosis were confirmed.

Blood Cells

Immunopathogenesis of human gastrointestinal infection by Anisakis simplex.

BACKGROUND: Anisakis simplex is a parasite of fish, and in the case of human infestation, it should be considered as a possible cause of gastrointestinal disease, especially in countries where raw or undercooked fish is a frequent food. Clinical features of anisakiasis may simulate acute abdominal pain, such as that found in patients with gastric ulcers, appendicitis, and Crohn's disease. Furthermore, many cases of anisakiasis are diagnosed as eosinophilic gastroenteritis, which is a broad term for a specific disease. OBJECTIVE: The purpose of this study was to investigate the immunopathogenesis of human gastrointestinal infestation by A simplex. METHODS: Thirteen intestinal biopsy specimens from patients with anisakiasis were analyzed for the presence of messenger (m)RNA for different cytokines and inflammatory mediators by RT-PCR. Specific IgE, eosinophil cationic protein, eosinophil protein X, and tryptase levels were measured in each patient's serum. Also, cell cultures were set up with lymphocytes from some patients and stimulated in vitro with Anisakis and Ascaris antigens. RESULTS: We performed immunologic phenotyping in 13 patients. All patients underwent biopsy after emergency surgery caused by episodes of acute abdominal pain. In all cases inflammatory infiltrate composed of eosinophils and lymphocytes was found in the intestinal wall. We demonstrated that after infestation, a T(H2)-type immune response occurred. Also, major basic protein, nitric oxide, and eotaxin were found in the tissue, and eosinophil cationic protein and eosinophil protein X levels were elevated in sera. CONCLUSION: These data and in vitro lymphocyte cultures indicate that a T(H2) mechanism plays an important role in the inflammatory infiltrate produced by the anchorage of parasites in the gastrointestinal wall.

Abdominal Pain

Beer-induced anaphylaxis: identification of allergens.

BACKGROUND: We report on a 21-year-old atopic woman who developed urticaria, angioedema of the face, and wheezy dyspnea shortly after drinking beer and after eating a corn-made snack. METHODS: Skin prick tests and specific IgE determinations to beer ingredients and cereal extracts were performed. Immunoblotting inhibition assays were carried out to investigate possible common allergens shared by barley and malt with corn. RESULTS: Skin prick tests and specific IgE measurements with beer, barley, malt, wheat, corn, rye, rice, and oat flour were positive. Ten pollen-allergic patients showed negative skin tests to beer. Double-blind, placebo-controlled, oral challenge tests with sodium metabisulfite and wheat flour were negative. Immunoblotting demonstrated several IgE-binding bands at 31-56 kDa in malt and barley extracts, and a major band at 38 kDa in the beer extract. Immunoblot inhibition assays showed that malt extract was able to inhibit most of the IgE-binding bands in wheat and corn extracts, whereas corn did not produce significant inhibition to barley and malt extracts. CONCLUSIONS: This patient developed type I hypersensitivity to barley/malt and corn. Although she also showed IgE reactivity to wheat and other cereals, no symptoms were elicited upon ingestion of these cereals, probably indicating latent sensitization to them.

Administration, Oral

Allergy to goat and sheep cheese with good tolerance to cow cheese.

BACKGROUND: We report on a patient who experienced allergic reactions after eating goat cheese and after touching goat and sheep cheese, but not after consuming cow's milk dairy products. OBJECTIVE: To assess the allergenicity and IgE-binding capacity of the caseins from the three different species. METHODS: Skin prick tests were carried out using whole milk and caseins from three different species (goat, sheep and cow), and whey fractions of cow's milk. Total serum IgE and specific IgE to cow's milk proteins were measured by CAP system and specific IgE against caseins and whole milk were determined by ELISA technique. To evaluate allergenic cross-reactivity, inhibition of the IgE ELISA activity to goat's milk and goat casein was tested for the three caseins. SDS-PAGE and immunoblotting was used to determine IgE binding bands in caseins. RESULTS: Skin tests were positive to sheep and goat's milk, sheep and goat casein, as well as to sheep and goat cheese. Total serum IgE was 66 kU/L and IgE determinations by CAP were negative. IgE ELISA against the caseins from goat and sheep was strongly positive, whereas it was negative to cow casein. ELISA inhibition assays revealed a high degree of cross-reactivity between goat casein and sheep casein. Immunoblotting showed three IgE-binding bands in goat casein at 31, 27 and 22 kDa, which may correspond to alpha-, beta- and gamma-caseins. A band at about 31 kDa was observed in sheep casein and another band at 34 kDa was recognized in cow casein. CONCLUSION: This patient developed allergy to goat and sheep cheese with good tolerance to cow's milk. We identified goat casein as the main allergen causing sensitization in this patient as demonstrated by in vivo and in vitro tests. A high degree of cross-reactivity between goat and sheep casein was observed.

Allergens

Aspirin inhibits inducible nitric oxide synthase expression and tumour necrosis factor-alpha release by cultured smooth muscle cells.

BACKGROUND: Inflammatory related cardiovascular disease, i.e. cardiac allograft rejection, myocarditis, septic shock, are accompanied by cytokine production, which stimulates the expression of inducible nitric oxide (iNOS). MATERIALS AND METHODS: The aim of the present study was to examine whether anti-inflammatory doses of acetylsalicylic acid (aspirin) could regulate iNOS protein expression in bovine vascular smooth muscle cells (BVSMCs) in culture. RESULTS: Interleukin 1 beta (IL-1 beta, 0.03 U mL-1) induced nitric oxide release by BVSMCs. Aspirin inhibited nitric oxide release from IL-1 beta-stimulated BVSMCs in a dose-dependent manner. In addition, aspirin significantly inhibited iNOS protein expression in BVSMCs and reduced the translocation of the nuclear factor-kappa B (NF-kappa B). Furthermore, aspirin and the blockade of NO generation by BVSMCs reduced the production of tumour necrosis factor alpha (TNF-alpha) by these cells. CONCLUSION: High doses of aspirin inhibited iNOS protein expression in BVSMCs and decreased NF-kappa B mobilization. The inhibition of iNOS expression by aspirin was further associated with a reduced ability of BVSMCs to produce TNF-alpha. This study could provide new mechanisms of action for aspirin in the treatment of the inflammation-related cardiovascular diseases.

6-Ketoprostaglandin F1 alpha

[Huntington chorea: clniical and molecular analysis in Asturian patients].

UNLABELLED: AIM AND PATIENTS: To analyse 38 patients with Huntington's disease from 27 families. RESULTS: The CAG repeat at the huntingtin gene was expanded between 40 and 72 times. The size in normal chromosomes varied from 12 to 30 repeats. We found a significantly negative correlation between the number of CAG-repeats and the age of clinical manifestations. However, age and clinical characteristics of the first symptoms were highly variable between patients with a similar size of the expanded allele. Patients who inherited the disease from their fathers showed a higher number of repeats than those who received the disease from their mothers. However, in one case of father to son transmission we observed a reduction of the number of CAG repeats. CONCLUSIONS: These data make it difficult to use the molecular analysis for the presymptomatic diagnosis of clinical course in individuals carrying the expansion.

Adolescent

Galectin-3 down-regulates IL-5 gene expression on different cell types.

Galectin-3 is an animal lectin, formerly named epsilon-binding protein or Mac-2, which has been described to play an important role in some inflammatory processes by the implication of different cells and the increase in cell adhesion functions through laminin binding activity. In this work we analyzed the role of galectin-3 in the modulation of Th2 cytokines that have an important role in the development of the inflammatory response. We have found that the addition of galectin-3 to human eosinophils, the eosinophilic cell line EoL-3, PBMC, and an Ag-specific T cell line (CD4+) produced a selective inhibition of IL-5 transcription. No inhibitory effect was found on the IL-4 mRNA transcription rate. The inhibitory effect on IL-5 transcription was reversed by incubation with lactose and using specific Ab against galectin-3. Galectin-3 is able to induce inhibition of the IL-5 released in the supernatants from PBMC stimulated with phorbol 12,13-dibutyrate and anti-CD3. Similar results were obtained when a T-specific cell line was stimulated with Ag. Also, EoL-3 stimulated with anti-CD32 produced IL-5 protein, the synthesis of which was partially inhibited by galectin-3. The present results demonstrate that galectin-3 induces a selective down-regulation of IL-5 expression in different cell types, opening important new possibilities in the regulation of the allergic reactions.

Antigens, Differentiation

[Effects of dietary fat saturation on levels of plasma lipoprotein (a) and lipids].

BACKGROUND: Lipoprotein (a) (Lp[a]) is a known risk factor for coronary heart disease. Lp(a) plasma concentration mainly depends on genetic polymorphism. The aim of this study was evaluate the effect of dietary fat saturation on Lp(a) plasma concentration. SUBJECTS AND METHODS: Forty two subjects (eighteen women and twenty four men) were placed in four consecutive 5 weeks diet periods. Energy intake from proteins, carbohydrates and fats was constant during the study and there were only changes on fatty acids composition. First period was enriched in saturated fatty acids (SFA), second period in monounsaturated fatty acids (MUFA) and third and fourth periods were enriched in polyunsaturated fatty acids (PUFA). Fourth period was also enriched in PUFA n-3 (blue fish). RESULTS: Changes on dietary fat saturation had a significant effect on plasma lipids and lipoproteins. Lp(a) plasma concentration was minimum in SFA phase (6.8 [SD 7.3] mg/dl), increasing during MUFA phase (8.7 [8.5] mg/dl) and was maximum in PUFA n-6 and PUFA n-3 (11.5 [11.1] and 12.7 [11.9] mg/dl, respectively) (p < 0.0001). CONCLUSIONS: Changes on dietary fat saturation significantly modify Lp(a) plasma concentration. These variations went in opposite direction to LDL-cholesterol modifications and were clinically irrelevant.

Adult

Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse.

High doses of glucocorticoids (GCs) are widely employed to treat acute attacks in relapsing-remitting multiple sclerosis (MS) patients. Their beneficial effects are partially due to their capacity to regulate the cytokine network. In the present work, we have examined the effect of GCs on the production of the immunosuppressor cytokine IL-10. Blood samples from MS patients suffering an acute relapse were obtained immediately before initiating therapy and after receiving a daily dose of 1 g intravenous methylprednisolone (MP) for four days. Levels of IL-10 mRNA in PBMC were semiquantified by RT-PCR, whereas protein concentration in serum and in cell culture supernatant was measured by ELISA. Our results show that 7 out of the 9 patients studied displayed increased IL-10 mRNA expression as well as higher serum IL-10 concentration following steroid treatment. In contrast, mRNA expression of two inflammatory cytokines, TNFalpha and IFNgamma, decreased following steroid therapy. In vitro experiments employing normal PBMC showed that methylprednisolone (MP) upregulated IL-10 expression as determined by measuring mRNA levels, flow cytometry of intracytoplasmic protein concentration, and the amount of secreted protein. Peak responses of secreted IL-10 by PBMC cultured cells treated with MP were obtained at 48 h. The effect was steroid-specific as IL-10 expression reversed to baseline levels in the presence of the glucocorticoid receptor antagonist RU486. Contrary to the effect of MP on the spontaneous expression of IL-10, this drug downregulated LPS-induced IL-10 synthesis. In fact, the concentration of IL-10 in LPS-induced IL-10 secretion from normal PBMC decreased upon addition of MP to cell cultures. Thus, it seems that MP exerts an opposite effect on the spontaneous and LPS-induced IL-10 production. Our studies indicate that GCs may control inflammatory responses by upregulating production of the immunosuppressor cytokine IL-10.

Acute Disease

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Adult