PubMed | Hospital Universitario La Paz, University of Granada, Hospital Universitario Marques Of Valdecilla, Complejo Hospitalario Badajoz and 10 more.
Type: | Journal: Frontiers in neurology | Year: 2016
Meniere disease (MD) is a heterogeneous clinical condition characterized by sensorineural hearing loss, episodic vestibular symptoms, and tinnitus associated with several comorbidities, such as migraine or autoimmune disorders (AD). The frequency of bilateral involvement may range from 5 to 50%, and it depends on the duration of the disease. We have performed a two-step cluster analysis in 398 patients with bilateral MD (BMD) to identify the best predictors to define clinical subgroups with a potential different etiology to improve the phenotyping of BMD and to develop new treatments. We have defined five clinical variants in BMD. Group 1 is the most frequently found, includes 46% of patients, and is defined by metachronic hearing loss without migraine and without AD. Group 2 is found in 17% of patients, and it is defined by synchronic hearing loss without migraine or AD. Group 3, with 13% of patients, is characterized by familial MD, while group 4, that includes 12% of patients, is associated by the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by AD. This approach can be helpful in selecting patients for genetic and clinical research. However, further studies will be required to improve the phenotyping in these clinical variants for a better understanding of the diverse etiological factors contributing to BMD.
Huergo-Zapico L.,University of Oviedo |
Gonzalez-Rodriguez A.P.,Hospital Cabuenes |
Contesti J.,Hospital Cabuenes |
Gonzalez E.,Hospital Cabuenes |
And 8 more authors.
Cancer Immunology, Immunotherapy | Year: 2012
MICA is a ligand of the activating receptor NKG2D, expressed by NK and T cells. MICA expression is induced in cancer cells favoring their elimination by the immune system; however, many advanced tumors shed soluble MICA (sMICA), which impairs NKG2D-mediated cytotoxicity. ERp5 and GRP78 are endoplasmic reticulumresident proteins that are translocated to the surface of epithelial tumor cells where they interact with MICA and are involved in sMICA shedding. In this study, we analyze the role of ERp5 and GRP78 in sMICA shedding in chronic lymphocytic leukemia (CLL). ImmunoXuorescence and Xow cytometry analyses showed that ERp5 and GRP78 were signiWcantly expressed on the surface of B cells and leukemia cells, but they were not expressed on T cells. The expression of ERp5 and GRP78 was signiWcantly higher in leukemia cells than in B cells from controls. ERp5 and GRP78 co-localized with MICA on the surface of leukemia cells and the levels of expression of ERp5 and GRP78 correlated with the level of expression of membrane-bound MICA in CLL patients. Associated with higher expression of membrane-bound ERp5 and GRP78, serum sMICA levels were approximately threefold higher in patients than in controls. Elevated sMICA levels in CLL patients were associated with the down-modulation of NKG2D surface expression on CD8 T cells. Finally, pharmacological inhibition of B cell lines and stimulated leukemia cells showed that ERp5 activity is involved in sMICA shedding in CLL. In conclusion, these results uncover a molecular mechanism which regulates MICA protein shedding and immune evasion in CLL. © Springer-Verlag 2012.
Huergo-Zapico L.,University of Oviedo |
Acebes-Huerta A.,University of Oviedo |
Gonzalez-Rodriguez A.P.,Hospital Universitario Central Of Asturias |
Contesti J.,Hospital Cabuenes |
And 6 more authors.
PLoS ONE | Year: 2014
The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL) which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CDS T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+ CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL. © 2014 Huergo-Zapico et al.
PubMed | Hospital Cabuenes, Hospital Universitario Central Of Asturias and University of Oviedo
Type: Journal Article | Journal: PloS one | Year: 2014
The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL) which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CD8 T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL.
Requena T.,University of Granada |
Espinosa-Sanchez J.M.,University of Granada |
Espinosa-Sanchez J.M.,Hospital San Agustin |
Cabrera S.,University of Granada |
And 13 more authors.
Clinical Genetics | Year: 2014
The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs) and offspring (λo) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PubMed | Hospital San Cecilio, Hospital Universitario La Paz, Hospital Cabuenes, Hospital Of Valme and 6 more.
Type: Journal Article | Journal: Seminars in arthritis and rheumatism | Year: 2015
To assess anti-TNF- therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy.Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF- therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load.A total of 17 patients (8 men; 29 affected eyes; mean standard deviation age 38.4 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF- therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 17.1 months. Significant improvement was observed following anti-TNF- therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 58.8 versus 247 40.5m) (p = 0.028), and visual acuity 0.60 0.33 versus 0.74 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF- therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load.Anti-TNF- therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.
PubMed | University of Granada, Complejo Hospitalario Badajoz, Complexo Hospitalario Universitario, Hospital Universitario Of Gran Canaria Dr Negrin and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2014
Menieres disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-B pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p=0.009 for rs3774937 and p=0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.
Arboleya S.,Institute Productos Lacteos Of Asturias Ipla Csic |
Solis G.,Paediatrics Service |
Fernandez N.,Hospital Cabuenes |
de los Reyes-Gavilan C.G.,Institute Productos Lacteos Of Asturias Ipla Csic |
Gueimonde M.,Institute Productos Lacteos Of Asturias Ipla Csic
Gut Microbes | Year: 2012
During recent years there has been an increasing interest on the development of strategies for modulating the process of microbiota establishment in preterm infants. For successfully developing of such strategies, a detailed knowledge of the microbiota establishment process in these infants is needed. In a previous study we evidenced clear alterations in the process of microbiota establishment in preterm newborns when compared with a control group of full-term breast-fed infants. Here we have analyzed these data more in depth, corroborating a reduced proportion of strict anaerobes with respect to facultatives in the fecal microbiota of preterm infants. The potential benefits, as well as the side effects, of strategies aimed at counterbalancing this alteration in the facultative to strict anaerobes ratio are discussed in this addendum. © 2012 Landes Bioscience.
Echarri P.P.,Institute of Diary Products of Asturias IPLA CSIC |
Echarri P.P.,University of Murcia |
Gracia C.M.,University of Murcia |
Berruezo G.R.,University of Murcia |
And 7 more authors.
Early Human Development | Year: 2011
The intestinal microbiota in the breast-fed infant is considered as ideally healthy. We assessed the microbiota of breast-fed full-term neonates from two different Spanish locations. Statistically significant geographical differences for different bacterial groups were found, underlining the need to consider and define geographical-related effects on microbiota. © 2011 Elsevier Ireland Ltd.
PubMed | Complejo Asistencial Universitario Of Leon, Hospital Alvarez Buylla and Hospital Cabuenes
Type: Journal Article | Journal: Archivos argentinos de pediatria | Year: 2015
It is common for pediatricians to provide parents with information on how to look after their newborn baby at the time of discharge from the hospital. The objectives of this study are to determine the level of satisfaction regarding such information, to be aware of what additional information parents would have liked to receive, and to establish which factors may impact any additional information request.Descriptive study evaluating the opinion of women at 5-15 days post- partum regarding such information.A hundred and seventy-six surveys were collected. Of these, 68.8% respondents had attended childbirth classes. Sixty-one point four percent referred to have looked for advice on the newborn infant care, mostly on the Internet and in books. Seventy-four point four percent considered that the information provided sufficed. Most commonly, information was requested on breastfeeding (33.3%), bottle feeding (20.0%), and umbilical cord care (11.1%). Mothers who requested more information attended childbirth classes more frequently (significant) and searched for information during pregnancy (not significant). In addition, this group significantly assigned a lower score to the opportunity to ask questions and the level of trust on the pediatrician.Maternal satisfaction regarding the information provided is adequate; and most mothers do not request additional information. The topic on which they most frequently request additional information is breastfeeding. The decision to request information does not depend on maternal age, maternal education, employment condition, or having other children. Likewise, mothers have questions that are not satisfactorily answered during childbirth classes.