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Sample records for cell deficient patients

  1. Polyclonal Expansion of NKG2C+ NK Cells in TAP-Deficient Patients

    Science.gov (United States)

    Béziat, Vivien; Sleiman, Marwan; Goodridge, Jodie P.; Kaarbø, Mari; Liu, Lisa L.; Rollag, Halvor; Ljunggren, Hans-Gustaf; Zimmer, Jacques; Malmberg, Karl-Johan

    2015-01-01

    Adaptive natural killer (NK) cell responses to human cytomegalovirus infection are characterized by the expansion of NKG2C+ NK cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs). Here, we set out to study the HLA class I dependency of such NKG2C+ NK cell expansions. We demonstrate the expansion of NKG2C+ NK cells in patients with transporter associated with antigen presentation (TAP) deficiency, who express less than 10% of normal HLA class I levels. In contrast to normal individuals, expanded NKG2C+ NK cell populations in TAP-deficient patients display a polyclonal KIR profile and remain hyporesponsive to HLA class I-negative target cells. Nonetheless, agonistic stimulation of NKG2C on NK cells from TAP-deficient patients yielded significant responses in terms of degranulation and cytokine production. Thus, while interactions with self-HLA class I molecules likely shape the KIR repertoire of expanding NKG2C+ NK cells during adaptive NK cell responses in normal individuals, they are not a prerequisite for NKG2C+ NK cell expansions to occur. The emergence of NKG2C-responsive adaptive NK cells in TAP-deficient patients may contribute to antiviral immunity and potentially explain these patients’ low incidence of severe viral infections. PMID:26500647

  2. Iron deficiency in sickle cell anaemia patients in Dar es Salaam ...

    African Journals Online (AJOL)

    A cross sectional descriptive study was done to determine the prevalence of iron deficiency and possible contributing factors in sickle cell anaemic patients. One hundred haemoglobin -SS children aged between six months to ten years inclusive were recruited in the study.Patients were selected using a simple random ...

  3. B-cell subsets in patients with transient hypogammaglobulinemia of infancy, partial IgA deficiency, and selective IgM deficiency.

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    Cipe, F E; Doğu, F; Güloğlu, D; Aytekin, C; Polat, M; Biyikli, Z; Ikincioğullari, A

    2013-01-01

    The pathogenesis of some primary humoral immunodeficiencies, such as transient hypogammaglobulinemia of infancy (THI) and immunoglobulin (Ig) A deficiency, remains unknown and can render diagnosis problematic. In the present study, we used flow cytometry to analyze peripheral blood B-cell subsets in patients with THI and unclassified hypogammaglobulinemia (UCH), partial IgA deficiency, and selective IgM deficiency. The study population comprised 41 patients with hypogammaglobulinemia (THI, 18; UCH, 23), 16 patients with partial IgA deficiency, and 16 patients with selective IgM deficiency who were admitted to Ankara University Department of Pediatric Immunology-Allergy between January 2010 and April 2011, as well as 29 healthy controls. B-cell subsets were examined according to the EUROclass classification. Age at diagnosis in the hypogammaglobulinemia group ranged between-14 months and 13 years (median, 26 months). Naive B-cell percentages were significantly higher and activated B-cell values lower in the THI patients than in the UCH patients and age-matched healthy controls. Nonswitched (IgM+CD27+IgD+) memory B-cell values were found to be significantly lower in patients with selective IgM deficiency than in healthy controls. No significant differences in B-cell subsets were found in patients with partial IgA deficiency. Previous reports show that reduced class-switched memory B cell values are associated with CVID, THI, and selective IgA deficiency. Our findings did not support these reports. Furthermore, we observed that naive B cell values were higher in patients with THI. A maturation defect could play a role in the pathogenesis of THI.

  4. Analysis of switched memory B cells in patients with IgA deficiency.

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    Aghamohammadi, Asghar; Abolhassani, Hassan; Biglari, Mohammad; Abolmaali, Sarah; Moazzami, Kasra; Tabatabaeiyan, Maryam; Asgarian-Omran, Hossein; Parvaneh, Nima; Mirahmadian, Mahroo; Rezaei, Nima

    2011-01-01

    Selective IgA deficiency (SIGAD) is the most common primary antibody deficiency, characterized by significant decreased serum levels of IgA in the presence of normal IgG and IgM. Despite several investigations into the nature of the disease, the exact pathophysiology of SIGAD is still unknown. In this study, switched memory B cells (CD19+/CD27+/IgD- cell population) of 28 patients with SIGAD and 28 matched healthy controls were investigated using flow cytometry. The percentage of switched memory B cells in all healthy controls was more than 0.4%. In SIGAD patients, who were classified as group I, the percentage of switched memory B cells was less than 0.4% (0.34 ± 0.06) in 7 patients (25%). The remaining 21 patients were designated as group II (1.74 ± 0.12%). The mean concentration of IgG in group I was significantly lower than in group II (1,014 ± 278 vs. 1,388 ± 406 mg/dl, p = 0.028). Comparison of clinical features between the 2 groups revealed that episodes of pneumonia during the course of disease were significantly higher in group I than in group II (p = 0.002). Autoimmune diseases in group I (57.1%) were also significantly higher (p = 0.01) than in group II (23.8%). The prevalence of bronchiectasis was 57% in group I, while only 1 patient (4.7%) in group II developed bronchiectasis (p = 0.006). Specific antibody deficiency in group I was documented in 5 patients and in group II in 4 patients (p = 0.01). The classification of SIGAD patients by assessment of switched memory B cells could help physicians with the clinical prognosis for these patients, whereas the patients with reduced switched memory B cells are prone to severe phenotypes. Copyright © 2011 S. Karger AG, Basel.

  5. A DEFICIENCY OF ANTIGEN-PRESENTING CELLS IN PATIENTS WITH PULMONARY TUBERCULOSIS

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    L. V. Sakhno

    2009-01-01

    Full Text Available Abstract. The phenotype and functional properties of antigen-presenting cells (APCs: blood monocytes and in vitro generated macrophages/dendritic cells were investigated in patients with pulmonary tuberculosis (TB, n = 192 with different levels of proliferative response to M. tuberculosis antigens (PPD-responsive vs PPD - anergic patients, n = 118 and 74, respectively. A functional deficiency of all 3 types of APCs was revealed in patients with TB. I.e., a monocyte disfunction was displayed by low CD86 and HLA-DR expression, 2-fold increase of CD14+CD16+ subset, high level of FasL+ and IL-10+ cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The in vitro generated macrophages from blood monocytes challenged with GM-CSF, were characterized by shifted Th1/Th2 balance (down-regulated production of IFNγ and IL-18 combined with up-regulation of IL-6 and IL-10, and reduced allostimulatory activity in mixed lymphocyte culture. The dendritic cells were characterized by decrease of mature, activated CD25+ cells, low level of IFNγ production in conjunction with enhanced capacity to produce IL - 10 and IL-6, and profound reduction of functional (allostimulatory activity. The APC disfunction of were most prominent in PPD-anergic patients. A possible role of APC disfunctions in disturbed antigen-specific T-cell response to M. tuberculosis is discussed.

  6. Evaluation of red cell and reticulocyte parameters as indicative of iron deficiency in patients with anemia of chronic disease

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    Ana Beatriz Barbosa Torino

    2014-12-01

    Full Text Available Objective:The purpose of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency.Methods:Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, and inflammatory activity, and the results of a hemoglobinopathy investigation as: iron deficiency anemia (n = 42, anemia of chronic disease (n = 28, anemia of chronic disease associated with iron deficiency anemia (n = 22, and heterozygous β thalassemia (n = 25. The percentage of microcytic red cells, hypochromic red cells, and levels of hemoglobin content in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating between the different types of anemia.Results:There was no significant difference between the iron deficient group and anemia of chronic disease associated with absolute iron deficiency in respect to any parameter. The percentage of hypochromic red cells was the best parameter to discriminate anemia of chronic disease with and without absolute iron deficiency (area under curve = 0.785; 95% confidence interval: 0.661–0.909, with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%. The formula microcytic red cells minus hypochromic red cells was very accurate in differentiating iron deficiency anemia and heterozygous β thalassemia (area under curve = 0.977; 95% confidence interval: 0.950–1.005; with sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8.Conclusion:The indices related to red cells and reticulocytes have a moderate performance in identifying absolute iron deficiency in patients with anemia of chronic disease.

  7. Zinc and antioxidant vitamin deficiency in patients with severe sickle cell anemia

    International Nuclear Information System (INIS)

    Hasanato, R.M. W.

    2006-01-01

    Patients with severe sickle cell anemia (SCA) have a higher potential for oxidative damage due to chronic redox imbalance in red blood cells that often leads to hemolysis, endothelial injury and recurrent vaso-occlusive episodes. This study evaluated the plasma levels of Vitamin A, C and E as indicators of antioxidants status. In addition, serum levels of zinc and copper were also estimated. Twenty-five adult patients with severe sickle cell anemia (12 males and 13 females aged 29.72+-12.94 years) and 25 matched controls were studied. Plasma levels of vitamin A, C and E were measured by HPLC technique. Serum zinc and copper levels were measured by atomic absorption spectrometry. There was significant decrease in plasma levels of vitamins A, C and E and in serum levels of zinc in patients with SCA as compared with controls (P<0.0001). Serum copper levels were significantly elevated compared with controls (P<0.0001). These findings emphasized the significant deficiencies of the antioxidant vitamins A, C and E and the trace element zinc along with the significant elevation of serum copper in patients with severe sickle cell disease. Further studies are needed to find out whether supplementation of antioxidant vitamins and zinc may ameliorate some sickle cell disease complications. (author)

  8. Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients

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    Raquel Ruiz-García

    2017-07-01

    Full Text Available GATA binding protein 2 (GATA2 deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients’ NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.

  9. Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE).

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    Bonelli, Michael; Savitskaya, Anastasia; von Dalwigk, Karolina; Steiner, Carl Walter; Aletaha, Daniel; Smolen, Josef S; Scheinecker, Clemens

    2008-07-01

    The objective of the study was that the regulatory T cells (Treg) that specialize in the suppression of immune responses might be critically involved in the pathogenesis of autoimmune disease. As for systemic lupus erythematosus (SLE), however, published data concerning Treg phenotype and function are partly conflicting. We therefore performed quantitative and qualitative analyses of naturally occurring CD4(+)CD25(+) Treg from SLE patients as compared with healthy controls (HC) in order to further elucidate the role of Treg in this systemic autoimmune disease. The phenotype of peripheral blood CD4(+)CD25(+) Treg was determined by flow cytometry (FACS) in SLE patients and HC. Treg were isolated from SLE patients and HC and their functional capacity was analyzed in suppression assays. Phenotypic and functional data were correlated with clinical data. Decreased proportions of CD4(+) Treg with high-level expression of CD25 (CD4(+)CD25(hi)) were observed in active and inactive SLE patients (0.96 +/- 0.08 and 1.17 +/- 0.08%, respectively) as compared with HC (2 +/- 0.1%). In contrast to HC, Treg from SLE patients displayed an activated phenotype as determined by the expression of CD69, CD71 and HLA-DR. The suppressive capacity of isolated Treg from SLE patients, however, was significantly reduced as compared with HC. Proportions of CD4(+)CD25(hi) T cells and the suppressive capacity of Treg were inversely correlated with the clinical disease activity in SLE patients. Our data describe quantitative and qualitative defects of Treg in SLE patients. These deficiencies might contribute to the breakdown of self-tolerance and the development of the autoimmune response in SLE patients.

  10. Terminally differentiated memory T cells are increased in patients with common variable immunodeficiency and selective IgA deficiency

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    Jana Nechvatalova

    2017-10-01

    Full Text Available Introduction : Previous studies showed that several lymphocyte abnormalities seen in the most frequent symptomatic immunoglobulin deficiency, common variable immunodeficiency (CVID, were also observed in a genetically related asymptomatic disorder – selective IgA deficiency (IgAD. In this study we searched for abnormalities in the differentiation stages of T cells as well as for similarities of these abnormalities in CVID and IgAD patients. Material and methods : Using flow cytometry in 80 patients with IgAD, 48 patients with CVID, and 80 control persons we determined T-lymphocyte subsets: both CD4 and CD8 were divided into the naïve CD45RO–CD27 + , early differentiated CD45RO + CD27 + , late differentiated CD45RO + CD27– and fully differentiated effector CD45RO–CD27– memory T cells, as well as Treg cells, defined as CD4 + CD25highCD127low T cells. Results : An increase of CD4 + and CD8 + late differentiated memory cells was observed comparing CVID patients to controls, as well as comparing IgAD patients to controls. In CVID patients an increase of CD4 + early differentiated memory cells, a decrease of CD8 + intermediate memory cells, and CD4 + and CD8 + naïve cells were found as well. The abnormalities in IgAD patients might be explained by higher CMV seropositivity observed in our IgAD. We confirmed the repeatedly published decrease of Treg cells in CVID patients, while Treg cells in IgAD patients were increased compared to controls. Conclusions : Our results show T-cell activation not only in CVID, but also in IgAD patients. The increase in IgAD patients may be influenced by a more frequent CMV infection in our group of IgAD patients.

  11. Terminally differentiated memory T cells are increased in patients with common variable immunodeficiency and selective IgA deficiency.

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    Nechvatalova, Jana; Pavlik, Tomas; Litzman, Jiri; Vlkova, Marcela

    2017-01-01

    Previous studies showed that several lymphocyte abnormalities seen in the most frequent symptomatic immunoglobulin deficiency, common variable immunodeficiency (CVID), were also observed in a genetically related asymptomatic disorder - selective IgA deficiency (IgAD). In this study we searched for abnormalities in the differentiation stages of T cells as well as for similarities of these abnormalities in CVID and IgAD patients. Using flow cytometry in 80 patients with IgAD, 48 patients with CVID, and 80 control persons we determined T-lymphocyte subsets: both CD4 and CD8 were divided into the naïve CD45RO - CD27 + , early differentiated CD45RO + CD27 + , late differentiated CD45RO + CD27 - and fully differentiated effector CD45RO - CD27 - memory T cells, as well as Treg cells, defined as CD4 + CD25highCD127low T cells. An increase of CD4 + and CD8 + late differentiated memory cells was observed comparing CVID patients to controls, as well as comparing IgAD patients to controls. In CVID patients an increase of CD4 + early differentiated memory cells, a decrease of CD8 + intermediate memory cells, and CD4 + and CD8 + naïve cells were found as well. The abnormalities in IgAD patients might be explained by higher CMV seropositivity observed in our IgAD. We confirmed the repeatedly published decrease of Treg cells in CVID patients, while Treg cells in IgAD patients were increased compared to controls. Our results show T-cell activation not only in CVID, but also in IgAD patients. The increase in IgAD patients may be influenced by a more frequent CMV infection in our group of IgAD patients.

  12. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

    Science.gov (United States)

    2017-12-03

    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  13. Prevalence of nutrient deficiencies in bariatric patients.

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    Toh, Seok Yee; Zarshenas, Nazy; Jorgensen, John

    2009-01-01

    The aims of this study were to determine the prevalence of nutrient deficiencies in patients who present for bariatric surgery, assess nutritional status after surgery, and compare these with preoperative levels. A retrospective study was conducted to identify preoperative and 1-year postoperative nutrition deficiencies in patients undergoing bariatric surgery. The screening included serum ferritin, vitamin D, vitamin B(12), homocysteine, folate, red blood cell folate, and hemoglobin. Results were available for 232 patients preoperatively and 149 patients postoperatively. Two-tailed chi(2) tests and paired-sample t tests were used. Preoperatively, vitamin D deficiency was noted at 57%. The prevalence of abnormalities 1 year after roux-en-Y gastric bypass was higher compared with preoperative levels (P surgery, anemia was detected in 17%, elevated homocysteine levels (women only) in 29%, low ferritin in 15%, low vitamin B(12) in 11%, and low RBC folate in 12%. Mean hemoglobin, ferritin, and RBC folate levels deteriorated significantly but remained well within normal ranges. The prevalence of vitamin D deficiencies decreased, but not significantly. In sleeve gastrectomy patients, mean ferritin levels decreased (P deficiency. Vitamin D deficiency is common among morbidly obese patients seeking bariatric surgery. Because the prevalence of micronutrient deficiencies persists or worsens postoperatively, routine nutrition screening, recommendation of appropriate supplements, and monitoring adherence are imperative in this population.

  14. Expressional and functional studies of Wolframin, the gene function deficient in Wolfram syndrome, in mice and patient cells.

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    Philbrook, Christine; Fritz, Eberhard; Weiher, Hans

    2005-01-01

    Wolfram Syndrome is an autosomal recessive degenerative disorder of the neuroendocrine system. Diabetes mellitus is its lead symptom. Patients show mutations in the wolframin (WFS1) gene coding for a hydrophobic transmembrane protein of 890 amino acids. This protein was preliminarily localised in the endoplasmatic reticulum (ER) in cells of mice and rats. Mice lacking the WFS1 gene display degeneration of pancreatic beta-cells following induction of ER stress. We here used antibodies against substructures of the wolframin protein in order to analyse its expression and localisation. Expression was detected in both pancreatic beta-cells and the limbic system of mice. Using the rat insulinoma cell line RIN 5AH and fractionated mouse brain tissue, we confirmed wolframin localisation to the endoplasmic reticulum. Expression profiling on patient's primary fibroblasts revealed down-regulation of the diabetes associated plasma membrane glycoprotein (PC-1) gene, and up-regulation of fibulin-3, a gene connected to senescence. However, cell proliferation was indistinguishable from non-mutated cells. In contrast to data obtained on murine pancreatic islets, we found no increased apoptosis following induction of ER stress but rather by staurosporine treatment in the absence of WFS1 function. This indicates a new role of WFS1 deficiency in programmed cell death.

  15. Hematinic deficiencies and anemia statuses in anti-gastric parietal cell antibody-positive or all autoantibodies-negative erosive oral lichen planus patients.

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    Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yu-Hsueh; Su, Yu-Xuan; Tu, Yu-Kang; Sun, Andy

    2018-03-01

    Approximately 27% of erosive oral lichen planus (EOLP) patients have serum anti-gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA or EOLP itself was a significant factor that caused hematinic deficiencies and anemia statuses in GPCA-positive or autoantibodies-negative EOLP patients (GPCA + /EOLP and Abs - /EOLP patients). The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 41 GPCA + /EOLP patients, 198 Abs - /EOLP patients, and 184 healthy control subjects. GPCA + /EOLP patients had significantly lower mean Hb, iron (for women only), and vitamin B12 level as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. Moreover, GPCA + /EOLP patients had significantly lower serum vitamin B12 level and significantly higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than Abs - /EOLP patients. Furthermore, Abs - /EOLP patients did have significantly lower mean Hb, MCV, iron (for women only), vitamin B12, and folic acid levels as well as significantly greater frequencies of Hb and iron deficiencies than healthy control subjects. We conclude that serum GPCA is the major factor that causes vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA + /EOLP patients. Approximately 29-32% GPCA-positive EOLP patients have vitamin B12 deficiency or macrocytosis and about 23-25% vitamin B12 deficiency or macrocytosis EOLP patients have pernicious anemia. ELOP itself does play a significant role in causing anemia and hematinic deficiencies in Abs - /EOLP patients. Copyright © 2017. Published by Elsevier B.V.

  16. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and -negative oral mucosal disease patients with microcytosis

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    Hung-Pin Lin

    2017-08-01

    Conclusion: We conclude that GPCA in microcytosis patients' sera may have caused significantly lower mean vitamin B12 level as well as significantly higher mean RDW and serum homocysteine level in our GPCA+/microcytosis patients than in GPCA−/microcytosis patients. Herein, iron deficiency anemia was the most common type of anemia in anemic GPCA+/microcytosis and GPCA−/microcytosis patients.

  17. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity.

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    Chang, Julia Y-F; Chen, I-Chang; Wang, Yi-Ping; Wu, Yu-Hsueh; Chen, Hsin-Ming; Sun, Andy

    2016-11-01

    Serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are found in some erosive oral lichen planus (EOLP) patients. This study assessed whether serum GPCA, TGA and TMA and EOLP itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive EOLP patients with GPCA positivity (GPCA + /TGA/TMA/EOLP patients) or negativity (GPCA - /TGA/TMA/EOLP patients). The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 29 GPCA + /TGA/TMA/EOLP patients, 80 GPCA - /TGA/TMA/EOLP patients, 198 all antibodies-negative EOLP patients (Abs - /EOLP patients), and 218 healthy control individuals. GPCA + /TGA/TMA/EOLP patients had significantly lower mean Hb and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy controls. GPCA + /TGA/TMA/EOLP patients had significantly lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA - /TGA/TMA/EOLP patients. Furthermore, both GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients did have significantly lower mean Hb, MCV, and iron (for women only) levels, as well as significantly greater frequencies of Hb and iron deficiencies than healthy controls. However, there were no significant differences in measured blood data between GPCA - /TGA/TMA/EOLP and Abs - /EOLP patients. We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA + /TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA - /TGA/TMA/EOLP patients. Copyright © 2016. Published by Elsevier B.V.

  18. Iron deficiency in cancer patients

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    Flávio Augusto Naoum

    Full Text Available ABSTRACT Anemia is a frequent complication in cancer patients, both at diagnosis and during treatment, with a multifactorial etiology in most cases. Iron deficiency is among the most common causes of anemia in this setting and can develop in nearly half of patients with solid tumors and hematologic malignancies. Surprisingly, this fact is usually neglected by the attending physician in a way that proper and prompt investigation of the iron status is either not performed or postponed. In cancer patients, functional iron deficiency is the predominant mechanism, in which iron availability is reduced due to disease or the therapy-related inflammatory process. Hence, serum ferritin is not reliable in detecting iron deficiency in this setting, whereas transferrin saturation seems more appropriate for this purpose. Besides, lack of bioavailable iron can be further worsened by the use of erythropoiesis stimulating agents that increase iron utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre-existing anemia, leading to a decline in performance status and adherence to treatment, with possible implications in clinical outcome. Due to its frequency and importance, treatment of this condition is already recommended in many specialty guidelines and should be performed preferably with intravenous iron. The evidences regarding the efficacy of this treatment are solid, with response gain when combined with erythropoiesis stimulating agents and significant increments in hemoglobin as monotherapy. Among intravenous iron formulations, slow release preparations present more favorable pharmacological characteristics and efficacy in cancer patients.

  19. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in patients ...

    African Journals Online (AJOL)

    This is a study of Glucose-6-phosphate dehydrogenase(G6PD) deficiency in sickle cell anaemia patients attending the haematology clinic of the Jos University Teaching Hospital (JUTH), Jos- Nigeria. The prevalence of G6PD deficiency among the 130 sickle cell anaemia patients studied was found to be 18.5%. G6PD ...

  20. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients.

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    Gavanescu, Irina; Benoist, Christophe; Mathis, Diane

    2008-09-02

    Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

  1. Altered development of NKT cells, γδ T cells, CD8 T cells and NK cells in a PLZF deficient patient.

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    Maggie Eidson

    Full Text Available In mice, the transcription factor, PLZF, controls the development of effector functions in invariant NKT cells and a subset of NKT cell-like, γδ T cells. Here, we show that in human lymphocytes, in addition to invariant NKT cells, PLZF was also expressed in a large percentage of CD8+ and CD4+ T cells. Furthermore, PLZF was also found to be expressed in all γδ T cells and in all NK cells. Importantly, we show that in a donor lacking functional PLZF, all of these various lymphocyte populations were altered. Therefore, in contrast to mice, PLZF appears to control the development and/or function of a wide variety of human lymphocytes that represent more than 10% of the total PBMCs. Interestingly, the PLZF-expressing CD8+ T cell population was found to be expanded in the peripheral blood of patients with metastatic melanoma but was greatly diminished in patients with autoimmune disease.

  2. Deficient leukemia inhibitory factor signaling in muscle precursor cells from patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Broholm, Christa; Brandt, Claus; Schultz, Ninna S

    2012-01-01

    -stimulated cell proliferation and a decreased LIF-stimulated induction of the proliferation-promoting factors cyclin D1, JunB, and c-myc. SOCS3 protein was upregulated in diabetic myoblasts, and knockdown of SOCS3 rescued LIF-induced gene expression in diabetic myoblasts, whereas neither STAT1 or STAT3 signaling...

  3. Flu Vaccine Guidance for Patients with Immune Deficiency

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    ... Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This article ... should patients with immune deficiency be given the vaccine? Immune deficient patients have a decreased resistance to ...

  4. Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation.

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    von Bahr, L; Blennow, O; Alm, J; Björklund, A; Malmberg, K-J; Mougiakakos, D; Le Blanc, A; Oefner, P J; Labopin, M; Ljungman, P; Le Blanc, K

    2015-09-01

    Vitamin D has emerged as a central player in the immune system, with its deficiency being implicated in the pathogenesis of several autoimmune diseases, including chronic GvHD. This is a retrospective cohort analysis of 166 patients, who underwent allogeneic hematopoietic stem cell transplantation (HSCT) at the Karolinska University Hospital, evaluating GvHD, graft failure, infectious complications and survival after HSCT in relation to pre-transplantation vitamin D levels. Most of the patients were deficient in vitamin D before HSCT (median 42 nmol/L). In multivariate analysis, vitamin D level before HSCT was identified as a significant independent risk factor for development of cGvHD. The increased incidence of cGvHD was not coupled to better disease-free survival; instead there was a trend towards lower overall survival in the vitamin D-deficient patients. In addition, we found a significant correlation between vitamin D deficiency and incidence of CMV disease, with no case of CMV disease occurring in patients with sufficient levels of vitamin D before HSCT. Our results support a role of vitamin D in immune tolerance following HSCT. These findings could be highly relevant for the care of HSCT patients, and prospective, randomized studies on the effect of vitamin D supplementation are therefore needed.

  5. Vitamin D deficiency in preoperative bariatric surgery patients.

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    Gemmel, Kelly; Santry, Heena P; Prachand, Vivek N; Alverdy, John C

    2009-01-01

    Obese patients are at risk of hypovitaminosis D. This is particularly concerning for those considering bariatric surgery because of the risk of postoperative nutritional deficiency. We hypothesized that it is necessary to screen for vitamin D deficiency preoperatively and conducted a study to identify the patterns of vitamin D deficiency among prospective bariatric surgery patients. A retrospective analysis of available preoperative laboratory values was conducted for all consecutive patients (n = 312) scheduled to undergo bariatric surgery from January 2004 to October 2006. Of the 312 patients, 179 (57.4%) were deficient in vitamin D preoperatively (25-hydroxyvitamin D deficient; of the 156 white patients evaluated, 57 (36.5%) were vitamin D deficient; and of the 14 Hispanic patients evaluated, 11 (78.6%) were vitamin D deficient. We also evaluated serum red blood cell folate, vitamin B(12), and free retinol vitamin A levels preoperatively. Of the 312 patients, 39 (12.5%) were vitamin A deficient and 11 (3.5%) were vitamin B(12) deficient. No patient had a red blood cell folate deficiency. Patients with hypovitaminosis D were also checked for secondary hyperparathyroidism; 42 patients (23.5%) fit the criteria (parathyroid hormone levels >75 pg/mL). Many patients with low vitamin D levels were being considered for the duodenal switch procedure. The results of our study have shown that prospective bariatric surgery patients, particularly candidates for highly malabsorptive procedures, should be screened for hypovitaminosis D preoperatively. Our findings also showed that blacks are particularly at risk of vitamin D deficiency.

  6. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

    Directory of Open Access Journals (Sweden)

    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  7. Dietary recommendations in patients with deficiency anaemia

    Directory of Open Access Journals (Sweden)

    A. Santoyo-Sánchez

    2015-07-01

    Nutritionists should understand deficiency anaemia, and physicians, particularly general practitioners, should be aware of dietary requirements. In this article, therefore, both health care professionals have come together to briefly explain, with examples, the type of diet that should be recommended to patients with deficiency anaemia.

  8. Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity

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    Julia Y.-F. Chang

    2016-11-01

    Conclusion: We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA−/TGA/TMA/EOLP patients.

  9. Anemia and hematinic deficiencies in anti-gastric parietal cell antibody-positive or all autoantibodies-negative recurrent aphthous stomatitis patients

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    Hung-Pin Lin

    2017-02-01

    Conclusions: We conclude that serum GPCA plays a significant role in causing vitamin B12 deficiency and high MCV in GPCA+/RAS patients. RAS itself does play a significant role in causing anemia and hematinic deficiencies in both GPCA+/RAS and Abs−/RAS patients.

  10. Patient reported outcome in posttraumatic pituitary deficiency

    DEFF Research Database (Denmark)

    Klose, Marianne; Stochholm, Kirstine; Janukonyté, Jurgita

    2015-01-01

    . RESULTS: Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, although only partially confirmed after adjustment for demographic differences. Hypogonadotropic hypogonadism related to several QoL scores. Increasing impairments were...

  11. Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

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    Nadia Charfi

    2012-01-01

    Full Text Available Congenital adrenal hyperplasia (CAH describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs. Leydig cell tumors (LCTs are make up a very small number of all testicular tumors and can be difficult to distinguish from TARTs. This distinction is interesting because LCTs and TARTs require different therapeutic approaches. Hereby, we present an unusual case of a 19-year-old patient with CAH due to 11β-hydroxylase deficiency, who presented with TARTs and an epididymal Leydig cell tumor.

  12. Urethral adenocarcinoma in a mental deficiency patient.

    Science.gov (United States)

    Ramírez-Sevilla, Cristóbal; Llopis-Manzanera, Juan; Romero-Martín, José Antonio; García-Vidal, Olga

    2014-12-01

    To report the case of a urethral tumour in a patient with mental deficiency. Complete resection of the tumour was performed and the pathologic examination informed the presence of urethral adenocarcinoma. The patient is disease-free twelve months after surgery. Bibliographic review for diagnosis and treatment was performed.

  13. Histidine deficiency attenuates cell viability in rat intestinal epithelial cells by apoptosis via mitochondrial dysfunction

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    Tatsunobu Matsui, M.S.

    2017-06-01

    Conclusions: This is the first report showing that histidine deficiency reduced cell viability and induced apoptosis in IEC-6 cells, and that a small amount of histidine supplementation prevented and improved the IEC-6 cell injury. This is a potential new clinical treatment against intestinal and/or gastric cell injury that would improve the patient's quality of life.

  14. Reading deficiencies in older patients.

    Science.gov (United States)

    Jackson, R H; Davis, T C; Murphy, P; Bairnsfather, L E; George, R B

    1994-08-01

    To participate effectively in their health care, older patients often are expected to read a wide variety of materials, including written instructions, brochures, and consent forms. This study quantitates the reading ability of older patients and compares it to that of younger patients. Two hundred seventy-two patients 30 and older were selected from five outpatient clinics at a public teaching hospital and tested for objective reading ability using the Peabody Individual Achievement Test--Revised. The 76 patients 60 and older read significantly worse (grade level 2.9) than the 196 patients younger than 60 (grade level 5.8) (P < 0.0001). Older patients also completed significantly fewer years of school than younger patients (7.3 years versus 10.6 years). Analysis of variance for age categories 30-44, 45-59, 60-74, and 75 and older confirmed declining reading ability and educational status with advancing age. Multiple regression analysis helped show that an equation could be derived to predict reading ability from age, educational status, race, and sex, but the coefficient of determination was so low (r2 = 0.39) that it cannot be considered clinically useful for individual patients. In this study, older patients read significantly worse than younger patients, and a formula that combines age, race, sex, and educational status cannot reliably predict reading ability for individual patients. Most older patients read on a level so low that they cannot be expected to read most commonly used written materials. Routine testing of reading ability may allow more appropriate design and use of written materials.

  15. Vitamin D Deficiency in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.

    2013-01-01

    Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

  16. Predictor Variables of Developing Anterior Pituitary Deficiencies in a Group of Paediatric Patients with Central Diabetes Insipidus and Langerhans Cell Histiocytosis.

    Science.gov (United States)

    Vaiani, Elisa; Malossetti, Carmen; Vega, Lina Margarita; Zubizarreta, Pedro; Braier, Jorge; Belgorosky, Alicia

    2017-01-01

    Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Central diabetes insipidus (CDI) is the most frequent endocrine manifestation and is a known risk factor for the development of further anterior pituitary hormone deficiencies (APD). However, not all CDI patients develop APD, as observed during prolonged periods of follow-up. To find predictors of developing APD in LCH children with CDI followed in our institution. We retrospectively analysed 44 patients over a median period (quartiles) of 12.3 years (8.79-14.24). Patients were subdivided into group 1 and group 2, according to absence or presence of APD, respectively. The main variables studied were: (1) chronological age (CA) at LCH diagnosis, (2) the primary site of LCH at diagnosis: low risk (LR) and multisystemic risk organs, and (3) the presence of reactivation. Multivariate Cox regression analysis showed that APD was positively associated with CA at LCH diagnosis [relative risk (RR) 1.14, p < 0.01], the LR clinical form (RR 8.6, p < 0.03), and negatively associated with the presence of reactivations (RR 0.3, p < 0.01). Patients with older CA at LCH diagnosis, LR clinical forms, and fewer reactivation episodes might represent a subgroup of paediatric LCH CDI patients with a higher risk of developing APD. © 2016 S. Karger AG, Basel.

  17. Oligodendroglia from ADSL-deficient patient produce SAICAribotide and SAMP.

    Science.gov (United States)

    Zídková, L; Krijt, J; Sládková, J; Hlobilková, A; Magner, M; Zikánová, M; Kmoch, S; Friedecký, D; Zeman, J; Elleder, M; Adam, T

    2010-01-01

    Succinylpurines accumulate in the body fluids of patients with adenylosuccinate lyase (ADSL) deficiency but their source in the cerebrospinal fluid remains obscure. Study based on the incorporation of 13C-stable isotope-labeled glycine into cultured oligodendroglia from ADSL-deficient patient and the measurement of labeled products by LC/MS/MS showed total intracellular concentrations of succinylpurines from 45 to 99μmol/l and so these results suggest that these cells can be the source of the compounds in vivo. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Nielsen, Christian; Fisker, Niels

    2008-01-01

    and the patient had eosinophilia. These presentations are consistent with atypical severe combined immunodeficiency (SCID)/Omenn Syndrome and the diagnosis was confirmed by demonstration of homozygosity for the R841W mutation in the catalytic core of RAG1. Comparison of the patient's immunoglobulin heavy chain...... chromosome 14. CONCLUSION: We hypothesize that the R841W mutation causes a malfunction of RAG1 that has differential outcome on V(D)J recombination in B and T cells, as the patient had normal B cell numbers but suffered severe alpha-beta T-cell immunodeficiency.......INTRODUCTION: A 2.5-month old boy presented with recurrent wheezing, protracted diarrhea, erythrodermia, and failure to thrive. METHODS AND RESULTS: Laboratory analysis showed lymphocytopenia with severely reduced T-cell numbers but normal numbers of B and NK cells. Serum IgE was increased...

  19. Glycogen Synthesis in Glycogenin 1-Deficient Patients

    DEFF Research Database (Denmark)

    Krag, Thomas O; Ruiz-Ruiz, Cristina; Vissing, John

    2017-01-01

    Context: Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup...

  20. Vitamin D deficiency in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Beena Bansal

    2012-01-01

    Full Text Available Background : Vitamin D [(25(OHD] deficiency and insufficiency is common in patients with chronic kidney disease (CKD. 25(OHD has been found to have beneficial effects on bone, cardiovascular and immune functions. There are little data about vitamin D levels in Indian patients on dialysis. This study was undertaken to determine the vitamin D status of Indian CKD patients on hemodialysis. Materials and Methods : We included 45 patients on maintenance hemodialysis coming to Medanta, Medicity, Gurgaon. 25(OHD levels were measured with radioimmunoassay (Diasorin method and parathyroid hormone (PTH was measured using electrochemiluminiscence immunoassay (ECLIA. Results : The mean age of patients was 55 ± 13 years. 32/45 (71% were males. 23/45 (51% were diabetics. The median duration of hemodialysis was 5.5 months (range 1-74 months. 33/45 (74% patients were on thrice weekly hemodialysis. The mean level of vitamin D was 10.14 ± 8.7 ng/ml. Majority of the patients [43/45 (95.5%] were either vitamin D deficient or had insufficient levels. 40/45 (88.9% were vitamin D deficient (levels <20 ng/ml; of these, 29/40 (64.4% had severe vitamin D deficiency (levels <10 ng/ml and 3/45 (6.7% had insufficient levels (20-30 ng/ml of vitamin D. Only 2/45 (4.4% patients had normal levels of vitamin D. 23/45 (51% of patients were receiving calcitriol. The mean levels of serum calcium, phosphorus, alkaline phosphatase, and albumin were 8.8 ± 0.64 mg/dl, 5.0 ± 0.7 mg/dl, 126 ± 10.3 IU/l and 3.6 ± 0.62 g/dl, respectively. PTH levels ranged from 37 to 1066 pg/ml, and the median was 195.8 pg/ml. There was a weak correlation between 25(OHD levels and weight, sex, hemoglobin, albumin, alkaline phosphatase, and presence of diabetes. There was, however, no correlation with duration of dialysis or PTH levels. Conclusion : Vitamin D deficiency and insufficiency are universal in our hemodialysis patients, with severe vitamin D deficiency in two-third of patients.

  1. Spontaneous T cell mediated keratoconjunctivitis in Aire-deficient mice

    Science.gov (United States)

    Yeh, S; de Paiva, C S; Hwang, C S; Trinca, K; Lingappan, A; Rafati, J K; Farley, W J; Li, D-Q; Pflugfelder, S C

    2013-01-01

    Background/aims Patients with autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) develop severe keratoconjunctivitis, corneal scarring and visual loss, but the precise pathogenesis is unknown. This study evaluated the ocular surface immune cell environment, conjunctival goblet cell density and response to desiccating environmental stress of the autoimmune regulatory (Aire) gene knockout murine model of APECED. Methods Aire-deficient and wild type (WT) mice were subjected to desiccating stress from a drafty, low-humidity environment and pharmacological inhibition of tear secretion for 5 days. Immune cell populations (CD4+, CD8+, CD11b+, CD45+) and goblet cell density were measured in ocular surface tissues and meibomian glands, and compared with baseline values. Results Greater CD4+ T cell populations were observed in the conjunctival epithelium of Aire-deficient mice (pAPECED. PMID:19429577

  2. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.

    Science.gov (United States)

    Salzer, Elisabeth; Santos-Valente, Elisangela; Klaver, Stefanie; Ban, Sol A; Emminger, Wolfgang; Prengemann, Nina Kathrin; Garncarz, Wojciech; Müllauer, Leonhard; Kain, Renate; Boztug, Heidrun; Heitger, Andreas; Arbeiter, Klaus; Eitelberger, Franz; Seidel, Markus G; Holter, Wolfgang; Pollak, Arnold; Pickl, Winfried F; Förster-Waldl, Elisabeth; Boztug, Kaan

    2013-04-18

    Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

  3. Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

    Science.gov (United States)

    Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

    2017-08-01

    Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

  4. A study of anemia in human immunodeficiency virus patients: Estimating the prevalence, analyzing the causative effect of nutritional deficiencies, and correlating the degree of severity with CD4 cell counts

    Directory of Open Access Journals (Sweden)

    Ajay Panwar

    2016-01-01

    Full Text Available Background: Anemia is a common complication of human immunodeficiency virus (HIV infection. The role of iron, Vitamin B12, and folate deficiencies, which are otherwise most common causes of anemia, is not well-established in HIV patients. Several studies in India have shown that severe immunodeficiency is associated with higher grade of anemia, but correlation of CD4 cell counts with severity of anemia is not well-documented. Aims: The aims of the present study were: To estimate the point prevalence of anemia in HIV patients, to analyze the causative role of iron, Vitamin B12, and folate deficiencies in anemic HIV patients, and correlating the degree of severity of anemia with CD4 cell counts. Materials and Methods: This study was a cross-sectional study. The study group enrolled 103 consecutive HIV patients attending medical emergency, medical outpatient department, medical wards, and anti-retroviral therapy (ART center at a tertiary care medical center in North India. Study participation consisted of a single visit during which relevant data, including medical history, current medications, CD4 T-lymphocyte count, complete hemogram with red blood cell indices, peripheral smear picture, iron studies, serum Vitamin B12, serum folate and bone marrow studies, were recorded on a case report form. Anemia was classified according to the World Health Organization criteria. Data analysis was carried out using Microsoft Excel and Statistical Package for the Social Sciences software. Results: 86.4% (89/103 patients were found to be anemic. There was no significant difference in prevalence of anemia in ART-naive patients from those who were on ART (P > 0.05. Pearson′s correlation had shown a highly significant positive correlation of hemoglobin and CD4 cell counts in male patients (r = 0.418 as well as female patients (r = 0.565. Normocytic normochromic was the most common type of anemia in males (46% as well as females (42%. Significant iron deficiency

  5. AIRE deficiency leads to impaired iNKT cell development.

    Science.gov (United States)

    Lindh, Emma; Rosmaraki, Eleftheria; Berg, Louise; Brauner, Hanna; Karlsson, Mikael C I; Peltonen, Leena; Höglund, Petter; Winqvist, Ola

    2010-02-01

    Autoimmune Polyendocrine Syndrome type I (APS I) is caused by mutations in the Autoimmune Regulator gene (AIRE), and results in the immunological destruction of endocrine organs. Herein we have characterized the CD1d-restricted invariant NKT cells (iNKT) and NK cells in APS I patients and Aire(-/-) mice, two cell populations known to play a role in the regulation of autoimmune disease. We show that the frequency of circulating iNKT cells is reduced in APS I patients compared to healthy controls. In accordance with this, iNKT cells are significantly reduced in the thymus and peripheral organs of Aire(-/-) mice. Bone marrow transfer from wild type donors into lethally irradiated Aire(-/-) recipients led to a decreased iNKT cell population in the liver, suggesting an impaired development of iNKT cells in the absence of Aire expression in radio-resistant cells. In contrast to the iNKT cells, both conventional NK cells and thymus-derived NK cells were unaffected by Aire deficiency and differentiated normally in Aire(-/-) mice. Our results show that expression of Aire in radio-resistant cells is important for the development of iNKT cells, whereas NK cell development and function does not depend on Aire. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation.

    Science.gov (United States)

    Barut Selver, Özlem; Yağcı, Ayşe; Eğrilmez, Sait; Gürdal, Mehmet; Palamar, Melis; Çavuşoğlu, Türker; Ateş, Utku; Veral, Ali; Güven, Çağrı; Wolosin, Jose Mario

    2017-10-01

    The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane) for expansion. The outgrowth (cultivated limbal epithelial cells) is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory Practice using

  7. Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Özlem Barut Selver

    2017-12-01

    Full Text Available The cornea is the outermost tissue of the eye and it must be transparent for the maintenance of good visual function. The superficial epithelium of the cornea, which is renewed continuously by corneal stem cells, plays a critical role in the permanence of this transparency. These stem cells are localized at the cornea-conjunctival transition zone, referred to as the limbus. When this zone is affected/destroyed, limbal stem cell deficiency ensues. Loss of limbal stem cell function allows colonization of the corneal surface by conjunctival epithelium. Over 6 million people worldwide are affected by corneal blindness, and limbal stem cell deficiency is one of the main causes. Fortunately, it is becoming possible to recover vision by autologous transplantation of limbal cells obtained from the contralateral eye in unilateral cases. Due to the potential risks to the donor eye, only a small amount of tissue can be obtained, in which only 1-2% of the limbal epithelial cells are actually limbal stem cells. Vigorous attempts are being made to expand limbal stem cells in culture to preserve or even enrich the stem cell population. Ex vivo expanded limbal stem cell treatment in limbal stem cell deficiency was first reported in 1997. In the 20 years since, various protocols have been developed for the cultivation of limbal epithelial cells. It is still not clear which method promotes effective stem cell viability and this remains a subject of ongoing research. The most preferred technique for limbal cell culture is the explant culture model. In this approach, a small donor eye limbal biopsy is placed as an explant onto a biocompatible substrate (preferably human amniotic membrane for expansion. The outgrowth (cultivated limbal epithelial cells is then surgically transferred to the recipient eye. Due to changing regulations concerning cell-based therapy, the implementation of cultivated limbal epithelial transplantation in accordance with Good Laboratory

  8. Seven Patients With Transcobalamin Deficiency Diagnosed Between 2010 and 2014

    DEFF Research Database (Denmark)

    Yildirim, Zuhal K; Nexo, Ebba; Rupar, Tony

    2017-01-01

    Transcobalamin deficiency (OMIM 275350) is a rare autosomal recessive disease presenting with nonspecific clinical features in early infancy. We report the clinical and laboratory manifestations of 7 children diagnosed with transcobalamin deficiency. All patients were admitted between 2 and 4...

  9. Hereditary nonspherocytic hemolytic anemia caused by red cell glucose-6-phosphate isomerase (GPI) deficiency in two Portuguese patients: Clinical features and molecular study.

    Science.gov (United States)

    Manco, Licínio; Bento, Celeste; Victor, Bruno L; Pereira, Janet; Relvas, Luís; Brito, Rui M; Seabra, Carlos; Maia, Tabita M; Ribeiro, M Letícia

    2016-09-01

    Glucose-6-phosphate isomerase (GPI) deficiency cause hereditary nonspherocytic hemolytic anemia (HNSHA) of variable severity in individuals homozygous or compound heterozygous for mutations in GPI gene. This work presents clinical features and genotypic results of two patients of Portuguese origin with GPI deficiency. The patients suffer from a mild hemolytic anemia (Hb levels ranging from 10 to 12.7g/mL) associated with macrocytosis, reticulocytosis, hyperbilirubinemia, hyperferritinemia and slight splenomegaly. Genomic DNA sequencing revealed in one patient homozygosity for a new missense mutation in exon 3, c.260G>C (p.Gly87Ala), and in the second patient compound heterozygosity for the same missense mutation (p.Gly87Ala), along with a frameshift mutation resulting from a single nucleotide deletion in exon 14, c.1238delA (p.Gln413Arg fs*24). Mutation p.Gln413Arg fs*24 is the first frameshift null mutation to be described in GPI deficiency. Molecular modeling suggests that the structural change induced by the p.Gly87Ala pathogenic variant has direct impact in the structural arrangement of the region close to the active site of the enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  11. Autoimmunity in patients with selective IgA deficiency.

    Science.gov (United States)

    Abolhassani, H; Gharib, B; Shahinpour, S; Masoom, S N; Havaei, A; Mirminachi, B; Arandi, N; Torabi-Sagvand, B; Khazaei, H A; Mohammadi, J; Rezaei, N; Aghamohammadi, A

    2015-01-01

    Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deticiency. Patients with SIgAD have a greater risk of concomitant autoimmune disorders than healthy individuals. The exact mechanism underlying the relationship between autoimmunity and SIgAD is not fully understood. The aim of this study was to evaluate potential associations between autoimmunity and specific clinical or immunological findings in patients with SIgAD. The study population comprised 57 symptomatic patients (65% males) with confirmed SIgAD who were referred to our center. Demographic data and history of autoimmunity were recorded both for patients and for their relatives. Comprehensive clinical and laboratory examinations were performed to investigate autoimmune complications in all the patients. Autoimmune disorders were documented in 17 cases (29.8%; 9 males and 8 females). The most common manifestations were thyroiditis, vitiligo, and hemolytic anemia (3 cases each). Ten patients (17.5%) had a family history of autoimmunity. Significant associations were detected between autoimmunity and increased duration of follow-up (P = .003), serum level of IgM (P = .01), regulatory T-cell count (P = .03), and class-switched memory B-cell count (P = .01). Four cases of autoimmune SIgAD (23.5%) progressed to common variable immunodeficiency during the follow-up period (P = .006). Autoimmune disorders, autoimmune cytopenia, and Ig subclass deficiency can lead to severe clinical manifestations in patients with SIgAD. Therefore, immunologists and pediatricians should be aware of these conditions.

  12. Helicobacter pylori infection in patients with acquired immune deficiency syndrome.

    Science.gov (United States)

    Battan, R; Raviglione, M C; Palagiano, A; Boyle, J F; Sabatini, M T; Sayad, K; Ottaviano, L J

    1990-12-01

    A controlled study was conducted on patients with human immunodeficiency virus (HIV) infection referred for upper endoscopy to evaluate the prevalence of Helicobacter pylori (H. pylori) infection. Four different stains and culture for H. pylori were performed on biopsy specimens from the gastric antrum. Sixteen (40%) of 40 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were diagnosed to be infected with H. pylori versus 14 (39%) of 36 age-matched control patients. Eight of 15 AIDS/ARC patients without AIDS-related esophagogastroduodenal findings (53%) were infected with H. pylori versus 8/25 (32%) with endoscopic findings typical of AIDS. No invasion of the lamina propria by H. pylori was noted in any patient. Active chronic gastritis was present in 60% of AIDS/ARC patients and 61% of controls. Fifty-eight and 59%, respectively, of active chronic gastritis cases were infected with H. pylori. All the H. pylori infections, except one, were found in patients with chronic gastritis. In AIDS/ARC patients, H. pylori infection and active chronic gastritis are as common as in other patients referred for upper endoscopy. They may play a pathogenic role, especially when endoscopic AIDS-related findings are lacking. Cell-mediated immune deficiency does not appear to increase the risk of infection with H. pylori.

  13. Choline Deficiency Causes Colonic Type II Natural Killer T (NKT) Cell Loss and Alleviates Murine Colitis under Type I NKT Cell Deficiency.

    Science.gov (United States)

    Sagami, Shintaro; Ueno, Yoshitaka; Tanaka, Shinji; Fujita, Akira; Niitsu, Hiroaki; Hayashi, Ryohei; Hyogo, Hideyuki; Hinoi, Takao; Kitadai, Yasuhiko; Chayama, Kazuaki

    2017-01-01

    Serum levels of choline and its derivatives are lower in patients with inflammatory bowel disease (IBD) than in healthy individuals. However, the effect of choline deficiency on the severity of colitis has not been investigated. In the present study, we investigated the role of choline deficiency in dextran sulfate sodium (DSS)-induced colitis in mice. Methionine-choline-deficient (MCD) diet lowered the levels of type II natural killer T (NKT) cells in the colonic lamina propria, peritoneal cavity, and mesenteric lymph nodes, and increased the levels of type II NKT cells in the livers of wild-type B6 mice compared with that in mice fed a control (CTR) diet. The gene expression pattern of the chemokine receptor CXCR6, which promotes NKT cell accumulation, varied between colon and liver in a manner dependent on the changes in the type II NKT cell levels. To examine the role of type II NKT cells in colitis under choline-deficient conditions, we assessed the severity of DSS-induced colitis in type I NKT cell-deficient (Jα18-/-) or type I and type II NKT cell-deficient (CD1d-/-) mice fed the MCD or CTR diets. The MCD diet led to amelioration of inflammation, decreases in interferon (IFN)-γ and interleukin (IL)-4 secretion, and a decrease in the number of IFN-γ and IL-4-producing NKT cells in Jα18-/- mice but not in CD1d-/- mice. Finally, adaptive transfer of lymphocytes with type II NKT cells exacerbated DSS-induced colitis in Jα18-/- mice with MCD diet. These results suggest that choline deficiency causes proinflammatory type II NKT cell loss and alleviates DSS-induced colitis. Thus, inflammation in DSS-induced colitis under choline deficiency is caused by type II NKT cell-dependent mechanisms, including decreased type II NKT cell and proinflammatory cytokine levels.

  14. In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

  15. Secondary Carnitine Deficiency in Dialysis Patients: Shall We Supplement It?

    OpenAIRE

    Ronald J.A. Wanders; Tim Ulinski; Stephanie E. Reuter; Asha Moudgil

    2016-01-01

    Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2) facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnit...

  16. Molecular analysis of B-cell differentiation in selective or partial IgA deficiency.

    Science.gov (United States)

    Asano, T; Kaneko, H; Terada, T; Kasahara, Y; Fukao, T; Kasahara, K; Kondo, N

    2004-05-01

    Selective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Ialpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated Ialpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Ialpha germline, alpha circle transcripts and Calpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Ialpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.

  17. Analysis of TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure based on phenotype of dendritic cells and function of T lymphocytes

    Directory of Open Access Journals (Sweden)

    YIN Sihan

    2016-04-01

    Full Text Available ObjectiveTo summarize the traditional Chinese medicine (TCM deficiency and excess attributes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF, and to analyze its association with the phenotype of dendritic cells (DCs and T lymphocyte subsets. MethodsThe basic information, stages, and TCM syndromes of 30 patients who were diagnosed with HBV-ACLF in The First Affiliated Hospital of Hunan University of Chinese Medicine from March to November, 2012 were collected, and according to their deficiency and excess attributes, they were divided into excess group and deficiency group. Ten healthy volunteers were enrolled as the control group. Flow cytometry was used to measure the percentage of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rate of CD4+CD25highCD127low cells, as well as the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86 which were isolated from peripheral blood mononucleated cells, induced, and cultured in vitro, and its association with TCM deficiency and excess attributes. The t-test was used for comparison of normally distributed continuous data between groups, the Wilcoxon rank sum test was used for comparison of continuous data which were not normally distributed between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsCompared with the healthy control group, the HBV-ACLF patients showed significant reductions in the percentages of CD3+, CD4+, and CD8+ T lymphocytes in peripheral blood and the expression rates of DCs with phenotypes of CD1α, HLA-DR, CD80, CD83, and CD86, as well as a significant increase in the expression rate of CD4+CD25highCD127lowcells (all P<0.01. Compared with the excess group, the deficiency group showed significant reductions in the percentages of CD3+ and CD4+ T lymphocytes and the expression rate of CD4+CD25highCD127low cells (all P<0.05. Compared with the deficiency group, the

  18. Observation on the changes of serum erythropoietin (EPO) and ferritin (SF) levels after preserved red cells (PRC) transfusion in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Li Keqin; Lv Haijun; Li Xinghua

    2008-01-01

    Objective: To study the changes of serum EPO and SF levels after preserved red cells transfusion in patients with IDA. Methods: Serum EPO and SF levels were detected with RIA both before and after transfusing preserved red cells in 35 patients with IDA as well as in 30 controls. Results: Before transfusion serum EPO levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Transfusing preserved red cells is an effective treatment and has important role in clinical application. (authors)

  19. Replication fork stability confers chemoresistance in BRCA-deficient cells

    DEFF Research Database (Denmark)

    Chaudhuri, Arnab Ray; Callen, Elsa; Ding, Xia

    2016-01-01

    /4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11......Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3...... nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations...

  20. Treatment of pediatric burn patient having glucose-6-phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Vijay Y Bhatia

    2016-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common red cell enzymopathy found in humans. It clearly has an X-linked recessive inheritance with its prevalence varying from 0% to 27% in a different caste, ethnic, and linguistic groups. This deficiency may result in hemolytic anemia during stress, infection, and use of certain drugs. The use of topical silver sulfadiazine can produce hemolysis in patients having G6PD deficiency. Here, we describe one case successfully treated of pediatric burn of 25% of body surface area who was a known case of G6PD deficiency.

  1. Predictors of Vitamin D Deficiency in Predialysis Patients with Stage ...

    African Journals Online (AJOL)

    Objective: Vitamin D status and risk factors of Vitamin D deficiency in chronic kidney disease (CKD) patients in China have been seldom reported before. In this study, we aim to investigate serum 25‑hydroxyvitamin D [25(OH)D] status and find the predictors of Vitamin D deficiency in predialysis patients with Stage 3–5 CKDs ...

  2. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia.

    Science.gov (United States)

    Kelkitli, Engin; Ozturk, Nurinnisa; Aslan, Nevin Alayvaz; Kilic-Baygutalp, Nurcan; Bayraktutan, Zafer; Kurt, Nezahat; Bakan, Nuri; Bakan, Ebubekir

    2016-04-01

    Iron deficiency anemia (IDA) is a major public health problem especially in underdeveloped and developing countries. Zinc is the co-factor of several enzymes and plays a role in iron metabolism, so zinc deficiency is associated with IDA. In this study, it was aimed to investigate the relationship of symptoms of IDA and zinc deficiency in adult IDA patients. The study included 43 IDA patients and 43 healthy control subjects. All patients were asked to provide a detailed history and were subjected to a physical examination. The hematological parameters evaluated included hemoglobin (Hb); hematocrit (Ht); red blood cell (erythrocyte) count (RBC); and red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (МСН), mean corpuscular hemoglobin concentration (МСНС), and red cell distribution width (RDW). Anemia was defined according to the criteria defined by the World Health Organization (WHO). Serum zinc levels were measured in the flame unit of atomic absorption spectrophotometer. Symptoms attributed to iron deficiency or depletion, defined as fatigue, cardiopulmonary symptoms, mental manifestations, epithelial manifestations, and neuromuscular symptoms, were also recorded and categorized. Serum zinc levels were lower in anemic patients (103.51 ± 34.64 μ/dL) than in the control subjects (256.92 ± 88.54 μ/dL; mental manifestations (p  100 μ/dL. When the serum zinc level was compared with pica, no statistically significant correlation was found (p = 0.742). Zinc is a trace element that functions in several processes in the body, and zinc deficiency aggravates IDA symptoms. Measurement of zinc levels and supplementation if necessary should be considered for IDA patients.

  3. B12 deficiency increases with age in hospitalized patients: a study on 14,904 samples.

    Science.gov (United States)

    Mézière, Anthony; Audureau, Etienne; Vairelles, Stéphane; Krypciak, Sébastien; Dicko, Michèle; Monié, Marguerite; Giraudier, Stéphane

    2014-12-01

    Cobalamin deficiency is responsible for hematological, neurological, neurocognitive, and neuropsychiatric impairments and is a risk factor for cardiovascular diseases, particularly in the elderly people. In order to determine B12 status in old inpatients, a total number of 14,904 hospitalized patients in whom B12 measurements were performed in five hospitals in the Paris metropolitan area were included from January 1, 2011 to December 31, 2011. The aims of the study were to determine whether age had an impact on B12 and folate deficiencies and to evaluate correlations between B12 and biological parameters-folate, hemoglobin, mean cell volume, homocystein (tHcy)-and age. Patients were aged 70.3±19.5 years. Low B12 concentration ( 17 µmol/L), 20.4% had low folate concentration (folate 17 µmol/L), and 4.7% of patients were both functional B12 and folate deficient. The B12 or folate deficient patients had lower mean cell volume level than nondeficient patients. Increase in mean cell volume and tHcy concentrations with age and decrease in B12, folate, and hemoglobin levels with age were observed. Frequency of functional B12 deficiency was 9.6% in patients aged 30-60 years and 14.2% in patients over 90 years. Frequency of functional folate deficiency was 9.5% in 30-60 years and 12.1% in >90 years. In inpatients, functional B12 deficiency and functional folate deficiency increase with age and are not associated with anemia or macrocytosis. False vitamin B deficiencies are frequent. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Congenital CMV with LAD type 1 and NK cell deficiency.

    Science.gov (United States)

    Rai, Narendra; Thakur, Neha

    2013-08-01

    We report a rare case of congenital cytomegalovirus (CMV) in a patient who was subsequently diagnosed as leukocyte adhesion defect type 1 with natural killer cell deficiency. The clinical course was complicated by severe CMV pneumonitis during the newborn period. Thereafter the infant suffered from recurrent skin infections without pus formation, otitis media, and bronchopneumonia since 3 months of age. The patient had congenital CMV infection as urine and blood plasma was positive for CMV from day 12 onward. Neutrophil chemotaxis studies showed a decrease in directed chemotaxis. Neutrophils were dyspoetic and nonfunctional lacking HLA DR, CD11c, and CD18. Lymphocytes were polyclonal but lacked CD56, CD16, and surface membrane immunoglobulin.

  5. Prevalence and hematological indicators of G6PD deficiency in malaria-infected patients.

    Science.gov (United States)

    Kotepui, Manas; Uthaisar, Kwuntida; PhunPhuech, Bhukdee; Phiwklam, Nuoil

    2016-04-25

    This study aimed to evaluate the prevalence and alteration of hematological parameters in malaria patients with a glucose-6-phosphate dehydrogenase (G6PD) deficiency, in the western region of Thailand, an endemic region for malaria. Data about patients with malaria hospitalized between 2013 and 2015 were collected. Clinical and sociodemographic characteristics such as age and gender, diagnosis on admission, and parasitological results were mined from medical records of the laboratory unit of the Phop Phra Hospital in Tak Province, Thailand. Venous blood samples were collected at the time of admission to hospital to determine G6PD deficiency by fluorescence spot test and detect malaria parasites by thick and thin film examination. Other data such as complete blood count and parasite density were also collected and analyzed. Among the 245 malaria cases, 28 (11.4 %) were diagnosed as Plasmodium falciparum infections and 217 cases (88.6 %) were diagnosed as P. vivax infections. Seventeen (6.9 %) patients had a G6PD deficiency and 228 (93.1 %) patients did not have a G6PD deficiency. Prevalence of male patients with G6PD deficiency was higher than that of female patients (P G6PD deficiency, two (11.8 %) were infected with P. falciparum, while the remaining were infected with P. vivax. Malaria patients with a G6PD deficiency have higher monocyte counts (0.6 × 10(3)/μL) than those without a G6PD deficiency (0.33 × 10(3)/μL) (P G6PD deficiency have high monocyte counts. The association between G6PD status and monocyte counts was independent of age, gender, nationality, Plasmodium species, and parasite density (P G6PD deficiency in a malaria-endemic area. This study also supported the assertion that patients with G6PD-deficient red blood cells had no protection against the P. falciparum infection. In addition, malaria patients with a G6PD deficiency had higher monocyte counts than those without a G6PD deficiency. These findings will help to recognize and

  6. Acute folate deficiency in a critically ill patient

    NARCIS (Netherlands)

    Geerlings, S. E.; Rommes, J. H.; van Toorn, D. W.; Bakker, J.

    1997-01-01

    A 19-year-old male patient developed thrombocytopenia and leukopenia due to acute folate deficiency while recovering from a multiple organ failure syndrome. Risk factors for acute folate deficiency are extensive tissue damage due to sepsis, trauma or surgery and acute renal failure requiring renal

  7. Renal phenotypic investigations of megalin-deficient patients

    DEFF Research Database (Denmark)

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina

    2013-01-01

    analysis of proximal tubular function in megalin-deficient patients.MethodsDirect sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through...

  8. Acquired colour vision deficiency in patients receiving digoxin maintenance therapy

    OpenAIRE

    Lawrenson, J G; Kelly, C; Lawrenson, A L; Birch, J

    2002-01-01

    Background/aims: Disturbances of colour vision are a frequently reported sign of digoxin toxicity. The aim of this study was to investigate the incidence of acquired colour vision deficiency in elderly hospitalised patients receiving maintenance digoxin therapy.

  9. SBDS-deficiency results in deregulation of reactive oxygen species leading to increased cell death and decreased cell growth.

    Science.gov (United States)

    Ambekar, Chhaya; Das, Bikul; Yeger, Herman; Dror, Yigal

    2010-12-01

    Shwachman-Diamond syndrome (SDS) is characterized by reduced hematopoietic and exocrine pancreatic cell numbers and a marked propensity for leukemia. Most patients have mutations in the SBDS gene. We previously reported that SBDS-deficient cells overexpress Fas, undergo accelerated spontaneous and Fas-mediated apoptosis and grow slowly. However the mechanism of how SBDS regulates apoptosis remains unknown. Several studies have shown that reactive oxygen species (ROS) regulate cell growth and spontaneous and Fas-mediated cell death. Therefore, we hypothesized that SBDS-deficiency disrupts ROS regulation and subsequently increases sensitivity to Fas stimulation and reduced cell growth. SBDS was knocked down in HeLa cervical cancer cells and TF-1 myeloid cells using short hairpin RNA. ROS levels were evaluated by oxidation of 2',7'-dichlorodihydrofluorescein diacetate. Apoptosis and cell growth were evaluated with and without antioxidants by annexin V/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, respectively. We found that shRNA mediated SBDS-knockdown resulted in a significant increase in ROS levels compared to control cells. Fas stimulation further increased ROS levels in the SBDS-knockdown HeLa cells more than in the controls. Importantly, balancing ROS levels by antioxidants rescued SBDS-deficient cells from spontaneous and Fas-mediated apoptosis and reduced cell growth. ROS levels are increased in SBDS-deficient cells, which leads to increased apoptosis and decreased cell growth. Increased baseline and Fas-mediated ROS levels in SBDS-deficient cells can enhance the sensitivity to Fas stimulation. By balancing ROS levels, antioxidants can improve cell growth and survival in SBDS-deficient cells.

  10. Optic neuropathy in a patient with pyruvate dehydrogenase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Small, Juan E. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States); Gonzalez, Guido E. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States); Clinica Alemana de Santiago, Departmento de Imagenes, Santiago (Chile); Nagao, Karina E.; Walton, David S. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Ophthalmology, Boston, MA (United States); Caruso, Paul A. [Massachusetts Eye and Ear Infirmary and Harvard Medical School, Department of Radiology, Boston, MA (United States)

    2009-10-15

    Pyruvate dehydrogenase (PDH) deficiency is a genetic disorder of mitochondrial metabolism. The clinical manifestations range from severe neonatal lactic acidosis to chronic neurodegeneration. Optic neuropathy is an uncommon clinical sequela and the imaging findings of optic neuropathy in these patients have not previously been described. We present a patient with PDH deficiency with bilateral decreased vision in whom MRI demonstrated bilateral optic neuropathy and chiasmopathy. (orig.)

  11. Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension.

    Science.gov (United States)

    Edwards, Adrienne L; Gunningham, Sarah P; Clare, Geoffrey C; Hayman, Matthew W; Smith, Mark; Frampton, Christopher M A; Robinson, Bridget A; Troughton, Richard W; Beckert, Lutz E L

    2013-11-01

    Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown. This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival. Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

  12. HMG-CoA lyase (HL) gene: Cloning and characterization of the 5{prime} end of the mouse gene, gene targeting in ES cells, and demonstration of large deletions in three HL-deficient patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S.; Robert, M.F.; Mitchell, G.A. [Hopital Sainte-Justine, Quebec (Canada)] [and others

    1994-09-01

    3-hydroxy-3-methylglutaryl CoA lyase (HL) is a mitochondrial matrix enzyme which catalyzes the last step of leucine catabolism and of ketogenesis. Autosomal recessive HL deficiency in humans results in episodes of hypoglycemia and coma. We are interested in the pathophysiology of HL deficiency as a model for both amino acid and fatty acid inborn errors. We have cloned the human and mouse HL genes. In order to analyze the 5{prime} nontranslated region of mouse HL gene, we cloned and sequenced a 1.8 kb fragment containing the 5{prime} extremity including exon 1 and about 1.6 kb of 5{prime} nontranslated sequence. The region surrounding exon 1 is CpG-rich (66.4%). Using the criteria of West, the Observed/Expected ratio for CpG dinucleotides is 0.7 ({ge}0.6 is consistent with a CpG island). We are carrying out primer extension and RNase protection experiments to determine the transcription initiation site. We constructed a gene targeting vector by introducing the neomycin resistance gene into exon 2 of a 7.5 kb genomic subclone of the mouse HL gene. Targeting was performed by electroporating 10 mg linearized vector into 10{sup 7} ES cells and selecting for 12 days with G418. 5/228 colonies (2.2%) had homologous recombination as shown by PCR screening and Southern analysis. We are microinjecting the 5 targeted clones into blastocysts to create an HL-deficient mouse. To date we have obtained two chimeras with contributions of 95% and 55% from 129, by coat color estimates. Three of 27 (11%) of the HL-deficient patients studied were suggested by genomic Southern analysis to be homozygous for large intragenic deletions. We confirmed this and defined the boundaries using exonic PCR.

  13. Growth hormone deficiency in cleft lip and palate patients

    Directory of Open Access Journals (Sweden)

    Shahin AbdollahiFakhim

    2015-11-01

    Full Text Available Introduction: Failure to thrive (FTT is relatively common among cleft patients, most commonly attributed to feeding problems during the first months of life. Close association between midline clefts and pituitary gland abnormalities prompted us to determine the frequency of growth hormone deficiency in cleft patients, which is easily treated. Methods: Any cleft patient with FTT was studied and when the patient’s height was under the 3rd percentile of normal, growth hormone was checked after clonidine administration. Growth hormone was checked before and 30, 60 and 90 minutes after clonidine use. Results: Of 670 patients with cleft lip or palate, 31 patients (4% had some kind of growth retardation according to weight, height or head circumstance. Eighteen patients were under the 3rd percentile of normal height. Growth hormone deficiency was detected in 8 patients out of 18 patients and overall frequency of growth hormone deficiency among cleft patients with growth retardation was 25.8% (8 out of 31. Seven patients of 8 were male whereas one was female and half of the patients were syndromic. Conclusion: Cleft patients have many problems with normal feeding and all kind of support should be provided to achieve near-normal feeding and they should be monitored for normal growth. Any patient with growth retardation, especially height decrease, should be assessed for growth hormone deficiency.

  14. Chromosomal replication incompatibility in Dam methyltransferase deficient Escherichia coli cells

    DEFF Research Database (Denmark)

    Freiesleben, Ulrik Von

    1996-01-01

    Dam methyltransferase deficient Escherichia coli cells containing minichromosomes were constructed. Free plasmid DNA could not be detected in these cells and the minichromosomes were found to be integrated in multiple copies in the origin of replication (oriC) region of the host chromosome...

  15. Identifying activated T cells in reconstituted RAG deficient mice using retrovirally transduced Pax5 deficient pro-B cells.

    Directory of Open Access Journals (Sweden)

    Nadesan Gajendran

    Full Text Available Various methods have been used to identify activated T cells such as binding of MHC tetramers and expression of cell surface markers in addition to cytokine-based assays. In contrast to these published methods, we here describe a strategy to identify T cells that respond to any antigen and track the fate of these activated T cells. We constructed a retroviral double-reporter construct with enhanced green fluorescence protein (EGFP and a far-red fluorescent protein from Heteractis crispa (HcRed. LTR-driven EGFP expression was used to enrich and identify transduced cells, while HcRed expression is driven by the CD40Ligand (CD40L promoter, which is inducible and enables the identification and cell fate tracing of T cells that have responded to infection/inflammation. Pax5 deficient pro-B cells that can give rise to different hematopoietic cells like T cells, were retrovirally transduced with this double-reporter cassette and were used to reconstitute the T cell pool in RAG1 deficient mice that lack T and B cells. By using flow cytometry and histology, we identified activated T cells that had developed from Pax5 deficient pro-B cells and responded to infection with the bacterial pathogen Listeria monocytogenes. Microscopic examination of organ sections allowed visual identification of HcRed-expressing cells. To further characterize the immune response to a given stimuli, this strategy can be easily adapted to identify other cells of the hematopoietic system that respond to infection/inflammation. This can be achieved by using an inducible reporter, choosing the appropriate promoter, and reconstituting mice lacking cells of interest by injecting gene-modified Pax5 deficient pro-B cells.

  16. Secondary Carnitine Deficiency in Dialysis Patients: Shall We Supplement It?

    Directory of Open Access Journals (Sweden)

    Ronald J.A. Wanders

    2016-07-01

    Full Text Available Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2 facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnitine deficiency may result from fatty acid β-oxidation disorders, which are diagnosed via plasma acylcarnitine profiling, but also under other conditions including haemodialysis. Given the importance of the kidney in maintaining carnitine homeostasis, it is not unexpected that longterm haemodialysis treatment is associated with the development of secondary carnitine deficiency, characterised by low endogenous L-carnitine levels and accumulation of deleterious medium and long- chain acylcarnitines. These alterations in carnitine pool composition have been implicated in a number of dialysis-related disorders, including erythropoietin-resistant renal anaemia. The association between erythropoietin resistance and carnitine levels has been demonstrated, with the proportion of medium and long-chain acylcarnitines within the total plasma carnitine pool positively correlated with erythropoietin resistance. Recent research has demonstrated that carnitine supplementation results in a significant reduction in erythropoietin dose requirements in patients with erythropoietin-resistant anaemia. Few studies have been conducted assessing the treatment of carnitine deficiency and haemodialysisrelated cardiac complications, particularly in children. Thus, a study was recently conducted which showed that intravenous carnitine in children receiving haemodialysis significantly increased plasma carnitine.

  17. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients

    International Nuclear Information System (INIS)

    Alangari, Abdullah; AlHarbi, Abdullah; AlGhonaium Abdulaziz; Santisteban, Ines; Hershfield, Michael

    2009-01-01

    Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity. (author)

  18. Urinary AASA excretion is elevated in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency

    NARCIS (Netherlands)

    Mills, P.B.; Footitt, E.J.; Ceyhan, S.; Waters, P.J.; Jakobs, C.A.J.M.; Clayton, P.T.; Struijs, E.A.

    2012-01-01

    Analysis of α-aminoadipic semialdehyde is an important tool in the diagnosis of antiquitin deficiency (pyridoxine-dependent epilepsy). However continuing use of this test has revealed that elevated urinary excretion of α-aminoadipic semialdehyde is not only found in patients with

  19. Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

    Science.gov (United States)

    Cheng, Chiung-Chi; Chao, Wei-Ting; Liao, Chen-Chun; Tseng, Yu-Hui; Lai, Yen-Chang Clark; Lai, Yih-Shyong; Hsu, Yung-Hsiang; Liu, Yi-Hsiang

    2018-01-02

    Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

  20. Neurotrophic keratitis in a patient with dihydroxypyrimidine dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Kapoor Bharat

    2008-01-01

    Full Text Available We describe a case of neurotrophic keratitis in association with dihydroxypyrimidine dehydrogenase (DHPD deficiency. Ocular manifestations in patients with DHPD are rare and neurotrophic keratitis has never been reported before. A six-year-old boy who was a known case of DHPD deficiency and born of a consanguineous marriage presented to our clinic with non-healing corneal ulcers in both eyes. Reduced corneal sensations were detected and the patient was started on lubricating eye drops. The patient continues to be on lubricant eye drops and there has been no recurrence of the disease.

  1. Vitamin D deficiency in patients with Behcet's disease.

    Science.gov (United States)

    Faezi, Seyedeh Tahereh; Ansari, Narges; Paragomi, Pedram; Akhlaghi, Maassoumeh; Ghanavat, Majid; Davatchi, Fereydoun

    2014-01-22

    Behcet's disease is an autoimmune, recurrent and multisystem disease. Vitamin D has immunomodulator role in immune system. So that vitamin D deficiency was reported in some autoimmune diseases. Behcet's disease as a Silk Road disease is common in Iran. The aim of this study was to detect the serum level of 25(OH) vitamin D in Behcet's patients and control group. In this case-control study, 112 Behcet's patients as cases group and 112 healthy individuals as controls group were enrolled. Any subject on vitamin D supplement, steroid, and immunosuppressors during the last 6 months were excluded. The serum level of 25(OH) vitamin D was measured in the two groups by ELISA method. The findings were compared via SPSS software. About 57% and 17% of Behcet's patients had vitamin D deficiency and insufficiency respectively. Vitamin D deficiency was significantly more common in controls than cases group (P Vitamin D levels were significantly lower in controls (P B5, and HLA-B51 with vitamin D level in Behcet's patients. Vitamin D deficiency is common among Behcet's patients. However, our results revealed vitamin D deficiency was significantly more common in healthy controls in comparison with Behcet's cases.

  2. Deficient natural killer cell function in preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  3. Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, Nicole; Fontana, Andrea O. [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland); Hug, Eugen B.; Lomax, Antony; Coray, Adolf [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Augsburger, Marc [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland); Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Sartori, Alessandro A. [Institute of Molecular Cancer Research, University of Zurich, Zurich (Switzerland); Pruschy, Martin, E-mail: martin.pruschy@usz.ch [Laboratory for Molecular Radiobiology, University Hospital Zurich, Zurich (Switzerland)

    2014-01-01

    Purpose: To investigate the impact of the 2 major DNA repair machineries on cellular survival in response to irradiation with the 2 types of ionizing radiation. Methods and Materials: The DNA repair and cell survival endpoints in wild-type, homologous recombination (HR)-deficient, and nonhomologous end-joining-deficient cells were analyzed after irradiation with clinically relevant, low-linear energy transfer (LET) protons and 200-keV photons. Results: All cell lines were more sensitive to proton irradiation compared with photon irradiation, despite no differences in the induction of DNA breaks. Interestingly, HR-deficient cells and wild-type cells with small interfering RNA-down-regulated Rad51 were markedly hypersensitive to proton irradiation, resulting in an increased relative biological effectiveness in comparison with the relative biological effectiveness determined in wild-type cells. In contrast, lack of nonhomologous end-joining did not result in hypersensitivity toward proton irradiation. Repair kinetics of DNA damage in wild-type cells were equal after both types of irradiation, although proton irradiation resulted in more lethal chromosomal aberrations. Finally, repair kinetics in HR-deficient cells were significantly delayed after proton irradiation, with elevated amounts of residual γH2AX foci after irradiation. Conclusion: Our data indicate a differential quality of DNA damage by proton versus photon irradiation, with a specific requirement for homologous recombination for DNA repair and enhanced cell survival. This has potential relevance for clinical stratification of patients carrying mutations in the DNA damage response pathways.

  4. Predictors of Vitamin D Deficiency in Predialysis Patients with Stage ...

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... this study, we aim to investigate serum 25-hydroxyvitamin D [25(OH)D] status and find the predictors of Vitamin D deficiency in predialysis patients with Stage. 3–5 CKDs in Southern China. Methods: In this retrospective cross-sectional study, hospitalized predialysis patients who were diagnosed of Stage ...

  5. Gastric emptying in patients with vitamin B12 deficiency

    International Nuclear Information System (INIS)

    Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf; Cingi, Elif; Kitapci, Mehmet

    2002-01-01

    The clinical presentation of patients with vitamin B 12 deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B 12 deficiency. The aim of this study was to evaluate the effect of vitamin B 12 deficiency on autonomic nervous system function by studying gastric emptying times (T 1/2 ). Twenty patients with newly diagnosed vitamin B 12 deficiency and 12 control patients with gastritis and normal vitamin B 12 levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B 12 replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T 1/2 in patients before and after treatment and in controls were 103.83±48.80 min, 90.00±17.29 min and 74.55±8.52 min, respectively. The difference in mean gastric emptying T 1/2 between patients before treatment and controls was statistically significant (P 12 treatment (P 1/2 was somewhat shorter. There were no positive or negative correlations between gastric emptying T 1/2 and the following parameters: haemoglobin, vitamin B 12 level and Helicobacter pylori positivity. In conclusion, gastric emptying T 1/2 was prolonged in patients with vitamin B 12 deficiency and this prolongation was not corrected after vitamin B 12 replacement therapy. Although autonomic nervous system dysfunction due to vitamin B 12 deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B 12 does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies. (orig.)

  6. Treatment of plasminogen deficiency patients with fresh frozen plasma.

    Science.gov (United States)

    Kızılocak, Hande; Ozdemir, Nihal; Dikme, Gürcan; Koç, Begüm; Atabek, Ayşe Ayzıt; Çokuğraş, Haluk; İskeleli, Güzin; Dönmez-Demir, Buket; Christiansen, Nina Merete; Ziegler, Maike; Ozdağ, Hilal; Schuster, Volker; Celkan, Tiraje

    2018-02-01

    Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment. © 2017 Wiley Periodicals, Inc.

  7. Iron deficiency anemia in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Goldberg ND

    2013-06-01

    Full Text Available Neil D Goldberg Emeritus Chief of Gastroenterology, University of Maryland St. Joseph Medical Center, Towson, MD, USA Abstract: Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%–76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient's quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented. Keywords: anemia, inflammatory bowel disease, intravenous iron, iron deficiency, oral iron, therapy

  8. Infrared assessment of knee instability in ACL deficient patients.

    Science.gov (United States)

    Matić, Aleksandar; Petrović Savić, Suzana; Ristić, Branko; Stevanović, Vladan B; Devedžić, Goran

    2016-02-01

    Previous clinical studies have shown that anterior cruciate ligament (ACL) ruptures require reconstructive surgery. The main goal of this study is an objective test definition for unstable knee diagnosis based on real measurements by using infrared cameras and adequate software. In the study of gait analysis 35 males with deficient ACL's participated. Pathological parameters for anterior posterior translation (APT) and internal external rotation (IER) and their values of kinematic data were obtained from a gait analysis 3D system. Movement curves were obtained by recording the position of fluorescent markers over time. A machine learning algorithm was developed in order to support decisions on the severity of the ACL injury and its corresponding deficiency. The algorithm was based on logistic regression. The value of APT, designated as exponentiation of the Ө coefficient (Exp (Ө)) of APT, showed that the likelihood of ACL-deficient knee occurrence due to higher values of APT is 1.1758 (95 % CI) times more frequent than that of the patients with lower values of APT. The value of IER, designated as Exp (Ө) of IER, showed that the patients with higher values of IER present 2.2516 (95 % CI) times higher values of ACL-deficient knee frequency than those with lower values. This study showed that the creation of ordered pairs of pathological parameters gives a wider picture of ACL deficiency and that such an algorithm may improve both examination and treatment of patients.

  9. Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells

    Science.gov (United States)

    Wang, Shan; He, Meifang; Li, Linmei; Liang, Zhihua; Zou, Zehong

    2016-01-01

    Purpose Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3. Methods We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines. Results Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis. Conclusion The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death. PMID:27721872

  10. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  11. Awareness of vitamin D deficiency among at-risk patients

    Directory of Open Access Journals (Sweden)

    Alemu Esubalew

    2012-01-01

    Full Text Available Abstract Background Vitamin D deficiency is a significant problem for a growing proportion of the UK population. Individuals with dark or covered skin are at particularly high risk due to ethno-cultural, environmental and genetic factors. We assessed the level of awareness of vitamin D deficiency among at-risk patients in order to identify groups most in need of education. Findings A cross-sectional survey using a piloted questionnaire was conducted among consecutive at-risk patients without a diagnosis of Vitamin D deficiency arriving at a large inner city general practice in the North West of England over a five day period. The survey was completed by 221 patients. The mean age was 35 years. 28% of them (n = 61 had never heard about vitamin D. Older patients (p = 0.003 were less likely to have heard about vitamin D. 54% of participants were unaware of the commonest symptoms of vitamin D deficiency. 34% did not expose their skin other than their face in the last one year, and 11% did not include vitamin D rich foods in their diet. Conclusion The majority of at-risk patients are aware of vitamin D; nevertheless, there is a significant lack of knowledge among older people, who have higher morbidity. A programme of targeted education of the at-risk population is recommended.

  12. Review of succinate dehydrogenase-deficient renal cell carcinoma with focus on clinical and pathobiological aspects

    Directory of Open Access Journals (Sweden)

    Naoto Kuroda

    2016-05-01

    Full Text Available Succinate dehydrogenase (SDH-deficient renal cell carcinoma (RCC was first identified in 2004 and has been integrated into the 2016 WHO classification of RCC. Succinate dehydrogenase (SDH is an enzyme complex composed of four protein subunits (SDHA, SDHB, SDHC and SDHD. The tumor which presents this enzyme mutation accounts for 0.05 to 0.2% of all renal carcinomas. Multiple tumors may occur in approximately 30% of affected patients. SDHB-deficient RCC is the most frequent, and the tumor histologically consists of cuboidal cells with eosinophilic cytoplasm, vacuolization, flocculent intracytoplasmic inclusion and indistinct cell borders. Ultrastructurally, the tumor contains abundant mitochondria. Immunohistochemically, tumor cells are positive for SDHA, but negative for SDHB in SDHB-, SDHC- and SDHD-deficient RCCs. However, SDHA-deficient RCC shows negativity for both SDHA and SDHB. In molecular genetic analyses, a germline mutation in the SDHB , SDHC or SDHD gene (in keeping with most patients having germline mutations in an SDH gene has been identified in patients with or without a family history of renal tumors, paraganglioma/pheochromocytoma or gastrointestinal stromal tumor. While most tumors are low grade, some tumors may behave in an aggressive fashion, particularly if they are high nuclear grade, and have coagulative necrosis or sarcomatoid differentiation.

  13. Iodine deficiency among goiter patients in rural South Sudan.

    Science.gov (United States)

    Chuot, Chep C; Galukande, Moses; Ibingira, Charles; Kisa, Nicholas; Fualal, Jane Odubu

    2014-10-23

    It is estimated that 2.2 billion or approximately 30% of the world's population live in iodine-deficient areas. In a 2005 study households consuming iodized salt in South Sudan increased from 40% to 73%. Despite this achievement, there are still many goiter cases in rural South Sudan and iodine deficiency remains as a major public health problem in this part of sub Saharan Africa.The purpose of this study therefore was to determine the prevalence of iodine deficiency among rural Southern Sudan goiter patients. A cross-sectional study was carried out in three South Sudan counties, adults with goiter were from three centers following a mobilization campaign that lasted 4 weeks for free medical care. They were clinically evaluated and completed interviewer administered questionnaires to determine their age, gender, diet, family history, drug history, and medical history. Urine samples were then taken for urinary iodine levels. The outcome was iodine deficiency measured as urinary iodine less than 100 μg per/ L. Multiple logistic regression was used to establish the factors associated with iodine deficiency in South Sudan. Ethical approval was obtained. A total of 286 goitre patients were recruited. The mean age was 38 years (SD 9), 262(92%) were females (F: M ratio 11:1), and 257(90%) were rural- peasants, 25% (20/286) had moderate to severe iodine deficiency. 174(62%) consumed non-iodized salts. Iodine deficiency is highly prevalent among rural South Sudan communities and a likely cause for goiters. Rural poor women are highly vulnerable.

  14. Glucose-6-phosphate dehydrogenase (G6PD-deficient epithelial cells are less tolerant to infection by Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Yi-Ting Hsieh

    Full Text Available Glucose-6-phosphate dehydrogenase (G6PD is a key enzyme in the pentose phosphate pathway and provides reducing energy to all cells by maintaining redox balance. The most common clinical manifestations in patients with G6PD deficiency are neonatal jaundice and acute hemolytic anemia. The effects of microbial infection in patients with G6PD deficiency primarily relate to the hemolytic anemia caused by Plasmodium or viral infections and the subsequent medication that is required. We are interested in studying the impact of bacterial infection in G6PD-deficient cells. G6PD knock down A549 lung carcinoma cells, together with the common pathogen Staphylococcus aureus, were employed in our cell infection model. Here, we demonstrate that a lower cell viability was observed among G6PD-deficient cells when compared to scramble controls upon bacterial infection using the MTT assay. A significant increase in the intracellular ROS was detected among S. aureus-infected G6PD-deficient cells by observing dichlorofluorescein (DCF intensity within cells under a fluorescence microscope and quantifying this signal using flow cytometry. The impairment of ROS removal is predicted to enhance apoptotic activity in G6PD-deficient cells, and this enhanced apoptosis was observed by annexin V/PI staining under a confocal fluorescence microscope and quantified by flow cytometry. A higher expression level of the intrinsic apoptotic initiator caspase-9, as well as the downstream effector caspase-3, was detected by Western blotting analysis of G6PD-deficient cells following bacterial infection. In conclusion, we propose that bacterial infection, perhaps the secreted S. aureus α-hemolysin in this case, promotes the accumulation of intracellular ROS in G6PD-deficient cells. This would trigger a stronger apoptotic activity through the intrinsic pathway thereby reducing cell viability when compared to wild type cells.

  15. Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens.

    Science.gov (United States)

    Brännström, Johan; Hässler, Signe; Peltonen, Leena; Herrmann, Björn; Winqvist, Ola

    2006-12-01

    Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.

  16. [Nutritional deficiencies in bariatric surgery patients: prevention, diagnosis and treatment].

    Science.gov (United States)

    Schweiger, Chaya; Keidar, Andrei

    2010-11-01

    The number of people suffering from surgery and obesity in the western world is constantly growing. In 1997 the World Health Organization (WHO) defined obesity as a plague and one of greatest public health hazards of our time. The National Institution of Health (NIH) declared that surgery is the only long-term solution for obesity. Today there are four different types of bariatric surgery. Each variation has different implications on the nutritional status of bariatric surgery patients. Bariatric surgery candidates are at risk of developing vitamin and mineral nutritional deficiencies in the post-operative stage, due to vomiting, decrease in food intake, food intolerance, diminution of gastric secretions and bypass of absorption area. It is easier and more efficient to treat nutritional deficiencies in the preoperative stage. Therefore, preoperative detection and correction are crucial. Blood tests before surgery to detect and treat nutritional deficiencies are crucial. In the postoperative period, blood tests should be conducted every 3 months in the first year after operation, every six months in the second year and annually thereafter. Multivitamin is recommended to prevent nutritional deficiencies in all bariatric surgery patients. Furthermore, iron, calcium, Vitamin D and B12 are additionally recommended for Roux-en-Y Gastric Bypass patients. Patients with Biliopancreatic diversion and Duodenal Switch should also take fat soluble vitamins.

  17. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S

    2010-01-01

    with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...

  18. Predictors of Vitamin D Deficiency in Predialysis Patients with Stage ...

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Female gender, hypoalbuminemia with serum albumin level <30.0 g/L, and severe damaged renal function with eGFR <30 ml/min/1.73 m2 are independent predictors of Vitamin D deficiency in predialysis patients with Stage 3–5 CKD. KEYWORDS: Chronic kidney disease, predialysis, predictors, Vitamin D ...

  19. Does the lateral intercondylar ridge disappear in ACL deficient patients?

    NARCIS (Netherlands)

    van Eck, Carola F.; Morse, Kenneth R.; Lesniak, Bryson P.; Kropf, Eric J.; Tranovich, Michael J.; van Dijk, C. Niek; Fu, Freddie H.

    2010-01-01

    The aim of this study was to determine whether there is a difference in the presence of the lateral intercondylar ridge and the lateral bifurcate ridge between patients with sub-acute and chronic ACL injuries. We hypothesized that the ridges would be present less often with chronic ACL deficiency.

  20. In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    Background: A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography–tandem mass spectrometry. Results: Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased

  1. Apoptosis and signalling in acid sphingomyelinase deficient cells

    Directory of Open Access Journals (Sweden)

    Sillence Dan J

    2001-11-01

    Full Text Available Abstract Background Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis. Hypothesis An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function. Testing the hypothesis It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes / lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype. Implications of the hypothesis If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.

  2. Vitamin D deficiency and insufficiency among patients with prostate cancer.

    Science.gov (United States)

    Trump, Donald L; Chadha, Manpreet K; Sunga, Annette Y; Fakih, Marwan G; Ashraf, Umeer; Silliman, Carrie G; Hollis, Bruce W; Nesline, Mary K; Tian, Lili; Tan, Wei; Johnson, Candace S

    2009-10-01

    To assess the frequency of vitamin D deficiency among men with prostate cancer, as considerable epidemiological, in vitro, in vivo and clinical data support an association between vitamin D deficiency and prostate cancer outcome. The study included 120 ambulatory men with recurrent prostate cancer and 50 with clinically localized prostate cancer who were evaluated and serum samples assayed for 25-OH vitamin D levels. Then 100 controls (both sexes), matched for age and season of serum sample, were chosen from a prospective serum banking protocol. The relationship between age, body mass index, disease stage, Eastern Cooperative Oncology Group performance status, season and previous therapy on vitamin D status were evaluated using univariate and multivariate analyses. The mean 25-OH vitamin D level was 25.9 ng/mL in those with recurrent disease, 27.5 ng/mL in men with clinically localized prostate cancer and 24.5 ng/mL in controls. The frequency of vitamin D deficiency (<20 ng/mL) and insufficiency (20-31 ng/mL) was 40% and 32% in men with recurrent prostate; 28% had vitamin D levels that were normal (32-100 ng/mL). Among men with localized prostate cancer, 18% were deficient, 50% were insufficient and 32% were normal. Among controls, 31% were deficient, 40% were insufficient and 29% were normal. Metastatic disease (P = 0.005) and season of blood sampling (winter/spring; P = 0.01) were associated with vitamin D deficiency in patients with prostate cancer, while age, race, performance status and body mass index were not. Vitamin D deficiency and insufficiency were common among men with prostate cancer and apparently normal controls in the western New York region.

  3. Vitamin D Deficiency in Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Suzan M. Attar

    2013-01-01

    Full Text Available Objectives: Hypovitaminosis D is common in the general population. Many studies that have been conducted to show the association between vitamin D deficiency and systemic lupus erythematosus (SLE reveal that deficiencies in vitamin D are common in this group of patients. Our aim was to study the relationship between 25(OHD and disease activity in patients with SLE.Methods: Retrospective cohort study of patients with SLE who were followed up at King Abdulaziz University Hospital, Jeddah, from January 2007 to November 2010. Demographic and clinical data were recorded and the 25(OHD levels of the patients were measured. Chi square tests, Student’s t-test, ANOVA and Pearson tests were used for data analysis. ANOVA test was followed by Bonferroni correction. A p-value <0.05 was considered significant.Results: Ninety-five patients with SLE were enrolled in the study. The levels of 25(OHD were significantly lower in patients with active SLE (n=41; 43% than in those with inactive disease (n=54; 57%; p=0.04. The mean (SD levels were 22.3 (14 nmol/L for patients with active disease against 25.0 (14 nmol/L for patients with inactive SLE. No correlation was detected between 25(OH D levels and disease activity score evaluated by SLEDAI-2K. By Pearson correlation, a significant negative correlation existed between 25(OH D and anti ds-DNA (r=-0.38; p<0.001; a positive correlation existed between 25(OHD levels and C4 (r=0.25; p=0.25. By chi square testing, azathioprine treatment (OR=3.5, low C4 (OR= 2.23, low C3 (OR=1.92, and active disease (OR=1.6 were associated with 25(OHD deficiency in SLE patients.Conclusion: Vitamin D deficiency is frequent in patients with SLE. Patients with SLE have a higher risk of developing 25(OHD deficiency in the presence of low serum C3 and C4 levels, and high anti-dsDNA levels.

  4. PARP Inhibition by Flavonoids Induced Selective Cell Killing to BRCA2-Deficient Cells

    Directory of Open Access Journals (Sweden)

    Cathy Su

    2017-10-01

    Full Text Available High consumption of dietary flavonoids might contribute to a reduction of cancer risks. Quercetin and its glycosides have PARP inhibitory effects and can induce selective cytotoxicity in BRCA2-deficient cells by synthetic lethality. We hypothesized that common flavonoids in diet naringenin, hesperetin and their glycosides have a similar structure to quercetin, which might have comparable PARP inhibitory effects, and can induce selective cytotoxicity in BRCA2-deficient cells. We utilized Chinese hamster V79 wild type, V-C8 BRCA2-deficient and its gene-complemented cells. In vitro analysis revealed that both naringenin and hesperetin present a PARP inhibitory effect. This inhibitory effect is less specific than for quercetin. Hesperetin was more cytotoxic to V79 cells than quercetin and naringenin based on colony formation assay. Quercetin and naringenin killed V-C8 cells with lower concentrations, and presented selective cytotoxicity to BRCA2-deficient cells. However, the cytotoxicity of hesperetin was similar among all three cell lines. Glycosyl flavonoids, isoquercetin and rutin as well as naringin showed selective cytotoxicity to BRCA2-deficient cells; hesperidin did not. These results suggest that flavonoids with the PARP inhibitory effect can cause synthetic lethality to BRCA2-deficient cells when other pathways are not the primary cause of death.

  5. Vitamin D deficiency in patients with liver cirrhosis.

    Science.gov (United States)

    Konstantakis, Christos; Tselekouni, Paraskevi; Kalafateli, Maria; Triantos, Christos

    2016-01-01

    There is ongoing evidence that vitamin D is related to the pathophysiology of cirrhosis. Although the incidence of vitamin D deficiency in chronic liver diseases and cirrhosis is strongly documented, its pathogenic association with advanced liver fibrosis remains controversial. There is evidence of a significant relation of 25(OH)D levels with the degree of liver dysfunction, considering that an inverse correlation of 25(OH)D levels with both Child-Pugh score and Model for End-Stage Liver Disease has been reported. In addition, vitamin D deficiency has been shown to increase the risk for overall mortality and infections in patients with cirrhosis. Vitamin D deficiency has been also associated with advanced stages of hepatocellular carcinoma and poor prognosis. Finally, there are studies suggesting that patients with chronic hepatitis C and normal vitamin D levels have higher virological response to treatment. However, there are not enough studies conducted in cirrhotic-only populations. The association between vitamin D and cirrhosis demonstrates a great potential for clinical application. The relation between vitamin D deficiency and the degree of liver function, degree of fibrosis and infectious complications could support its use as a prognostic index and a diagnostic tool.

  6. Prevalence of nutritional deficiency in patients with pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Silvana Gomes Nunes Piva

    2013-06-01

    Full Text Available OBJECTIVE: To determine the prevalence of nutritional deficiency among patients with pulmonary tuberculosis. METHODS: This was a cross-sectional study using data obtained from the Brazilian Case Registry Database and from the medical records of patients diagnosed with pulmonary tuberculosis (15-59 years of age residing in one of the municipalities that make up the 16th Regional Health District of the state of Bahia. We calculated the incidence, lethality, and mortality rates, as well as the prevalence of nutritional deficiency, as evaluated by body mass index. Demographic, social, clinical, and epidemiological data were collected. RESULTS: Of the 72 confirmed cases of tuberculosis, 59 (81.9% were in males, and 21 (29.2% of the patients were in the 40-49 year age bracket. The majority (85.3% described themselves as Mulatto or Black; 55.2% reported using alcohol; and approximately 90% were treated as outpatients. In the district and age bracket studied, the incidence of pulmonary tuberculosis was 30.6/100,000 population. Among the 72 patients, data regarding nutritional status was available for 34. Of those, 50% and 25%, respectively, presented nutritional deficiency at the beginning and at the end of treatment. No statistically significant differences were found between normal-weight and malnourished patients regarding the characteristics studied. CONCLUSIONS: The prevalence of nutritional deficiency was high among our sample of patients with pulmonary tuberculosis. This underscores the importance of nutritional follow-up for the assessment of tuberculosis treatment in the decision-making process regarding therapeutic interventions.

  7. Irradiation shortens the survival time of red cells deficient in glucose-6-phosphate dehydrogenasee

    Energy Technology Data Exchange (ETDEWEB)

    Westerman, M.P. (Rush Medical College, Chicago, IL); Wald, N.; Diloy-Puray, M.

    1980-03-01

    X radiation of glucose-6-phosphate dehydrogenase (G6PD)-deficient red cells causes distinct shortening of their survival time. This is accompanied by significant lowering of reduced glutathione content and is not observed in similarly prepared and treated normal cells. The damage is most likely related to irradiation-induced formation of activated oxygen products and to their subsequent effects on the cells. Neither methemoglobin increases nor Heinz body formation were observed, suggesting that hemolysis occurred prior to these changes. The study provides a model for examining the effects of irradiation and activated oxygen on red cells and suggests that patients with G6PD deficiency who receive irradiation could develop severe hemolysis in certain clinical settings.

  8. Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Johansen, J; Marker, O

    1996-01-01

    To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...

  9. Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes.

    Science.gov (United States)

    Turner, W J; Chatten, J; Lampson, L A

    1990-04-01

    We have examined two features of neuroblastoma cells that had not been well-characterized in a xenogeneic model: The cells display unusual immunologic properties in other experimental systems, and the original tumors display widespread and characteristic patterns of metastasis. To determine the most appropriate immunodeficient host for primary tumor growth, T cell-deficient nude mice, NK-deficient beige mice, beige-nudes, and controls were injected with the well-characterized line CHP-100. To define the pattern of tumor spread, complete autopsies were performed following subcutaneous, intraperitoneal and intravenous injections. CHP-100 consistently formed subcutaneous tumors in T cell-deficient mice (nude and beige-nude), but not in T cell-competent mice (beige, heterozygous nu/+ and bg/+, or wild-type). The growth rate and final size of the subcutaneous tumors were not greater in beige-nudes than in nudes. All mice showed early CHP-100 cell death after subcutaneous injection; the nature of the immunodeficiency was more relevant for the surviving subpopulation. Widespread dissemination was seen following intravenous injection, particularly in beige-nudes. Aspects of the growth patterns were appropriate to the tumor of origin. The behavior in immunodeficient mice suggests that T cells can play a role in controlling the growth of these cells; the next steps will be to define the effector mechanisms, and to determine if they can be exploited for human patients. The hematogenous spread following intravenous injection suggests that insights into the control of blood-borne tumor may also come from further study of this model.

  10. Targeting HIF2α Translation with Tempol in VHL-Deficient Clear Cell Renal Cell Carcinoma

    Science.gov (United States)

    Ghosh, Manik C.; Ghosh, Sanchari; Yang, Youfeng; Gupta, Gopal; DeGraff, William; Krishna, Murali C.; Mitchell, James B.; Rouault, Tracey A.; Linehan, W. Marston

    2012-01-01

    The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1α and HIF2α, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2α, but not HIF1α, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2α could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2α, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1α and HIF2α. We first evaluated the protein expression of HIF1α and HIF2α in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2α, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O2 compared to 5% O2, which may lower HIF2α expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2α in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels. PMID:23178531

  11. Survival and Psychomotor Development With Early Betaine Treatment in Patients With Severe Methylenetetrahydrofolate Reductase Deficiency

    NARCIS (Netherlands)

    Diekman, Eugene F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.; Rovers, Maroeska M.; van Hasselt, Peter M.

    IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

  12. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency

    NARCIS (Netherlands)

    Diekman, E.F.; Koning, T.J. de; Verhoeven-Duif, N.M.; Rovers, M.M.; Hasselt, P.M. van

    2014-01-01

    IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

  13. HepG2 cells develop signs of riboflavin deficiency within four days of culture in riboflavin-deficient medium*

    OpenAIRE

    Werner, Ricarda; Manthey, Karoline C.; Griffin, Jacob B.; Zempleni, Janos

    2005-01-01

    Flavin mononucleotide and flavin adenine dinucleotide are essential coenzymes in redox reactions. For example, flavin adenine dinucleotide is a coenzyme for both glutathione reductase and enzymes that mediate the oxidative folding of secretory proteins. Here we investigated short-term effects of moderately riboflavin-deficient culture medium on flavin-related responses in HepG2 hepatocarcinoma cells. Cells were cultured in riboflavin-deficient (3.1 nmol/L) medium for up to six days; controls ...

  14. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

    NARCIS (Netherlands)

    Gennery, A.R.; Slatter, M.A.; Rice, J.; Hoefsloot, L.H.; Barge, D.; McLean-Tooke, A.; Montgomery, T.; Goodship, J.A.; Burt, A.D.; Flood, T.J.; Abinun, M.; Cant, A.J.; Johnson, D.

    2008-01-01

    More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are

  15. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S

    2010-01-01

    with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...... vein with well expressed portosystemic collaterals, heterozygosity for three common polymorphisms in FVII gene, associated with reduction in plasma FVII levels, and no other factors predisposing to thrombosis....

  16. Cell Motility and Invasiveness of Neurofibromin-Deficient Neural Crest Cells and Malignant Triton Tumor Lines

    National Research Council Canada - National Science Library

    Vogel, Kristine S

    2005-01-01

    .... We have completed our analyses of NfI4- embryonic NOC invasiveness in vitro, and compared effects of neurofibromin deficiency in different embryonic mesenchymal cell populations derived from cranial and trunk regions...

  17. Anesthetic Management of a Pediatric Patient with Arginase Deficiency

    Directory of Open Access Journals (Sweden)

    Abdulkadir Atım

    2011-09-01

    Full Text Available Arginase deficiency is an autosomal recessive disorder of the urea cycle in which a defect in conversion of arginine to urea and ornithine leads to hyperammonemia. Patients with urea cycle disorders may show increased protein catabolism due to inadequate intake of energy, protein and essential amino acids; infections, fever and surgery. A 12-year-old girl with arginase deficiency, ASA II who weighed 40 kg was scheduled for bilateral adductor, quadriceps and gastrocnemius tenotomies. She had mental retardation, spasticity and flexion posture of thelower limbs. Metabolic homeostasis was restored with appropriate diet. Successful anesthetic management allowed the patient to be discharged 48 hours after surgery. Increased levels of arginine and ammonia during or after surgery may lead to serious complications such as hypotension, cerebral edema, convulsions, hypothermia and spasticity. Thus special attention must be given to metabolic homeostasis and nutrition of the patients with arginase deficiency in the perioperative period. Primary goals should be to minimize stress levels by effective anxiolysis, provide an adequate amount of protein-free energy with proper fluid management and to obtain an effective preemptive and postoperative analgesia. In addition to a high level of knowledge, successful anesthesia requires professional communication among nursing staff, dietitians, pediatric metabolism specialist, surgeon and anesthesiologist.

  18. Anisometropia and ptosis in patients with monocular elevation deficiency

    International Nuclear Information System (INIS)

    Zafar, S.N.; Islam, F.; Khan, A.M.

    2016-01-01

    Objective: To determine the effect of ptosis on the refractive error in eyes having monocular elevation deficiency Place and Duration of Study: Al-Shifa Trust Eye Hospital, Rawalpindi, from January 2011 to January 2014. Methodology: Visual acuity, refraction, orthoptic assessment and ptosis evaluation of all patients having monocular elevation deficiency (MED) were recorded. Shapiro-Wilk test was used for tests of normality. Median and interquartile range (IQR) was calculated for the data. Non-parametric variables were compared, using the Wilcoxon signed ranks test. P-values of <0.05 were considered significant. Results: A total of of 41 MED patients were assessed during the study period. Best corrected visual acuity (BCVA) and refractive error was compared between the eyes having MED and the unaffected eyes of the same patient. The refractive status of patients having ptosis with MED were also compared with those having MED without ptosis. Astigmatic correction and vision had significant difference between both the eyes of the patients. Vision was significantly different between the two eyes of patients in both the groups having either presence or absence of ptosis (p=0.04 and p < 0.001, respectively). Conclusion: Significant difference in vision and anisoastigmatism was noted between the two eyes of patients with MED in this study. The presence or absence of ptosis affected the vision but did not have a significant effect on the spherical equivalent (SE) and astigmatic correction between both the eyes. (author)

  19. Leydig Cell Tumor Associated with Testicular Adrenal Rest Tumors in a Patient with Congenital Adrenal Hyperplasia due to 11β-Hydroxylase Deficiency

    OpenAIRE

    Charfi, Nadia; Kamoun, Mahdi; Feki Mnif, Mouna; Mseddi, Neila; Mnif, Fatma; Kallel, Nozha; Ben Naceur, Basma; Rekik, Nabila; Fourati, Hela; Daoud, Emna; Mnif, Zainab; Hadj Sliman, Mourad; Sellami-Boudawara, Tahia; Abid, Mohamed

    2012-01-01

    Congenital adrenal hyperplasia (CAH) describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Chronic excessive adrenocorticotropic hormone (ACTH) stimulation may result in hyperplasia of ACTH-sensitive tissues in adrenal glands and other sites such as the testes, causing testicular masses known as testicular adrenal rest tumors (TARTs). Leydig cell tumors (...

  20. Examining the Association between Vitamin B12 Deficiency and Dementia in High-Risk Hospitalized Patients.

    Science.gov (United States)

    Siswanto, O; Smeall, K; Watson, T; Donnelly-Vanderloo, M; O'Connor, C; Foley, N; Madill, J

    2015-12-01

    To explore the association between vitamin B12 deficiency and dementia in patients at high risk for vitamin B12 deficiency. Chart review. Emergency, critical care/ trauma, neurology, medicine, and rehabilitation units of two hospitals in Southwestern Ontario, Canada. Adult patients (n = 666) admitted from 2010 to 2012. Data collection included: reason for admission, gender, age, clinical signs and symptoms of B12 deficiency, serum B12 concentration, and B12 supplementation. Patients with dementia were identified based on their medication profile and medical history. Vitamin B12 deficiency (pmol/L) was defined as serum B12 concentration 220. Comparisons between B12-deficient patients with and without dementia were examined using parametric and non-parametric tests. Serum B12 values were available for 60% (399/666) of the patients, of whom 4% (16/399) were B12-deficient and 14% (57/399) were marginally deficient. Patients with dementia were not more likely to be B12-deficient or marginally deficient [21% (26/121)] compared to those with no dementia [17% (47/278), p=0.27)]. Based on documentation, 34% (25/73) of the B12-deficient and marginally-deficient patients did not receive B12 supplementation, of whom 40% (10/25) had dementia. In this sample of patients, there was no association between B12 deficiency and dementia. However, appropriate B12 screening protocols are necessary for high risk patient to identify deficiency and then receive B12 supplementation as needed.

  1. Chromosomal replication incompatibility in Dam methyltransferase deficient Escherichia coli cells

    DEFF Research Database (Denmark)

    Freiesleben, Ulrik Von

    1996-01-01

    Dam methyltransferase deficient Escherichia coli cells containing minichromosomes were constructed. Free plasmid DNA could not be detected in these cells and the minichromosomes were found to be integrated in multiple copies in the origin of replication (oriC) region of the host chromosome....... The absence of the initiation cascade in Dam- cells is proposed to account for this observation of apparent incompatibility between plasmid and chromosomal copies of oriC. Studies using oriC-pBR322 chimeric plasmids and their deletion derivatives indicated that the incompatibility determinant is an intact...... in the oriC region of the chromosome, led to the conclusion that initiation of DNA replication commences at a fixed cell mass, irrespective of the number of origins contained on the chromosome....

  2. Genetic and immunologic analysis of a family containing five patients with common-variable immune deficiency or selective IgA deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Ashman, R.F.; Kemp, J.D.; Yokoyama, W.M. (Univ. of Iowa College of Medicine, Iowa City (United States)); Zhu, Z.B.; Cooper, M.D.; Volanakis, J.E. (Univ. of Alabama, Birmingham (United States))

    1992-11-01

    A family with 13 members included 2 subjects with selective IgA deficiency (IgA-D) and 3 subjects with common-variable immune deficiency (CVID), diseases which usually occur sporadically. Reciprocal combinations of B and T cells in vitro between one normal and two immune-deficient family members and normal subjects revealed that defective Ig synthesis was determined by the B cells, while the patient T cells functioned normally. Normal T helper and suppressor function was demonstrated even in one patient with CVID who developed a T-cell lymphoproliferative disorder associated with elevated IgM; this patient's B cells made only IgM in vitro. Immune deficiencies were inherited in this family in a pattern consistent with an autosomal dominant trait with incomplete penetrance. All the immune-deficient patients in this family possessed at least one copy of an MHC haplotype previously shown to be abnormally frequent in IgA-D and CVID: HLA-DQB1*0201, HLA-DR3, C4B-Sf, C4A-deleted, G11-15, Bf-0.4, C2-a, HSP70-7.5, TNF[alpha]-5, HLA-B8, and HLA-A1. The patient who developed the lymphoproliferative disorder was homozygous for this haplotype. Four immunologically normal members, one of whom was 80 years old, also possessed this MHC haplotype, indicating that its presence is not sufficient for disease expression. A small segment of another MHC haplotype associated with Ig deficiency in the population also occurred in this family, but it was not associated with immune deficiency. The presence of neutral amino acids at position 57 of DQ[beta], previously correlated with IgA-D, was associated with disease in this family approximately to the same degree reported previously in unrelated patients. Thus the expression of immunodeficiency in individuals bearing a disease-associated MHC haplotype appears to require either additional genes or an environmental trigger.

  3. Cardiovascular risk in patients with alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fähndrich, Sebastian; Biertz, Frank; Karch, Annika; Kleibrink, Björn; Koch, Armin; Teschler, Helmut; Welte, Tobias; Kauczor, Hans-Ulrich; Janciauskiene, Sabina; Jörres, Rudolf A; Greulich, Timm; Vogelmeier, Claus F; Bals, Robert

    2017-09-15

    Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATD-related lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET ("COPD and SYstemic consequences-COmorbidities NETwork") cohort focusing on the distribution of comorbidities. The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation.

  4. Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency

    OpenAIRE

    Shaw, Rachel K.; Issekutz, Andrew C.; Fraser, Robert; Schmit, Pierre; Morash, Barb; Monaco-Shawver, Linda; Orange, Jordan S.; Fernandez, Conrad V.

    2012-01-01

    EBV-associated smooth muscle tumors are found in immunocompromised patients, most commonly HIV/AIDS. We present a 12-year-old girl with the first documented case of EBV-related smooth muscle tumors in the presence of a rare classic NK cell deficiency. This sheds light on the role of NK cells in controlling EBV-related smooth muscle tumors.

  5. Protein C deficiency in a patient of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Tamzeed Ahmed

    2009-01-01

    Full Text Available A 42-year old male presented with acute myocardial infarction with no discernable risk factors; he never smoked; did not suffer from diabetes and had a well controlled blood pressure with single medication; plasma concentration of total cholesterol was on the upper normal limit, high and low density lipoprotein, cholesterol and triglyceride being normal. In addition to a single antihypertensive he received Allupurinol(Xanthine Oxidase inhibitorfor hyperuricaemia. Coronary angiogram revealed ectatic epicardial coronary arteries. The patient developed deep vein thrombosis of right leg after four days of the coronary angiogram. Coagulation analysis revealed protein C deficiency. The recognition of protein C deficiency as a risk factor for myocardial infarction is important as anticoagulators prevent further thrombotic events whereas inhibitors of platelet aggregation are ineffective. Ibrahim Med. Coll. J. 2009; 3(1: 34-35

  6. Myelography in patients with acquired immuno deficiency syndrome

    International Nuclear Information System (INIS)

    Borgstein, B.J.; Koster, P.A.; Peeters, F.L.M.; Portegies, P.

    1989-01-01

    Neurological complications in patients with Acquired Immuno Deficiency Syndrome (AIDS) are frequent and in addition to central nervous system syndromes, involvement of the peripheral nervous system is increasingly seen. We evaluated the indications and results of myelographic examination in six AIDS-patients with signs of peripheral nervous system disease, out of 200 AIDS-patients with neurological complications. Five of these patients had a polyradiculopathy, with proven cytomegalovirus (CMV) infection in four cases. There were two abnormal myelographic examinations with findings of cauda equina nerve root involvement, both in patients with proven CMV-polyradiculopathy. These abnormal findings had no direct therapeutic consequences. Myelography is not essential for establishing the diagnosis, which is based on cerebrospinal fluid (CSF) analysis, but may be indicated to exclude a spinal cord or nerve root compressive lesion. (orig.)

  7. Glycogen Synthesis in Glycogenin 1-Deficient Patients: A Role for Glycogenin 2 in Muscle.

    Science.gov (United States)

    Krag, Thomas O; Ruiz-Ruiz, Cristina; Vissing, John

    2017-08-01

    Glycogen storage disease (GSD) type XV is a rare disease caused by mutations in the GYG1 gene that codes for the core molecule of muscle glycogen, glycogenin 1. Nonetheless, glycogen is present in muscles of glycogenin 1-deficient patients, suggesting an alternative for glycogen buildup. A likely candidate is glycogenin 2, an isoform expressed in the liver and heart but not in healthy skeletal muscle. We wanted to investigate the formation of glycogen and changes in glycogen metabolism in patients with GSD type XV. Two patients with mutations in the GYG1 gene were investigated for histopathology, ultrastructure, and expression of proteins involved in glycogen synthesis and metabolism. Apart from occurrence of polyglucosan (PG) bodies in few fibers, glycogen appeared normal in most cells, and the concentration was normal in patients with GSD type XV. We found that glycogenin 1 was absent, but glycogenin 2 was present in the patients, whereas the opposite was the case in healthy controls. Electron microscopy revealed that glycogen was present between and not inside myofibrils in type II fibers, compromising the ultrastructure of these fibers, and only type I fibers contained PG bodies. We also found significant changes to the expression levels of several enzymes directly involved in glycogen and glucose metabolism. To our knowledge, this is the first report demonstrating expression of glycogenin 2 in glycogenin 1-deficient patients, suggesting that glycogenin 2 rescues the formation of glycogen in patients with glycogenin 1 deficiency. Copyright © 2017 Endocrine Society

  8. Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

    Directory of Open Access Journals (Sweden)

    Jahnavi Aluri

    2018-02-01

    Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

  9. Stem cell selection in vivo using foamy vectors cures canine pyruvate kinase deficiency.

    Directory of Open Access Journals (Sweden)

    Grant D Trobridge

    Full Text Available Hematopoietic stem cell (HSC gene therapy has cured immunodeficiencies including X-linked severe combined immunodeficiency (SCID-X1 and adenine deaminase deficiency (ADA. For these immunodeficiencies corrected cells have a selective advantage in vivo, and low numbers of gene-modified cells are sufficient to provide therapeutic benefit. Strategies to efficiently transduce and/or expand long-term repopulating cells in vivo are needed for treatment of diseases that require higher levels of corrected cells, such as hemoglobinopathies. Here we expanded corrected stem cells in vivo in a canine model of a severe erythroid disease, pyruvate kinase deficiency.We used a foamy virus (FV vector expressing the P140K mutant of methylguanine methyltransferase (MGMTP140K for in vivo expansion of corrected hematopoietic repopulating cells. FV vectors are attractive gene transfer vectors for hematopoietic stem cell gene therapy since they efficiently transduce repopulating cells and may be safer than more commonly used gammaretroviral vectors. Following transplantation with HSCs transduced ex vivo using a tri-cistronic FV vector that expressed EGFP, R-type pyruvate kinase, and MGMTP140K, we were able to increase marking from approximately 3.5% to 33% in myeloid long-term repopulating cells resulting in a functional cure.Here we describe in one affected dog a functional cure for a severe erythroid disease using stem cell selection in vivo. In addition to providing a potential cure for patients with pyruvate kinase deficiency, in vivo selection using foamy vectors with MGMTP140K has broad potential for several hematopoietic diseases including hemoglobinopathies.

  10. Complementing the patient: a complement component deficiency in a patient with recurrent infections and glomerulonephritis.

    Science.gov (United States)

    Sinclair, David; Wilde, Graeme; Bex, Samantha; Peters, Sheila

    2005-01-01

    We present a case showing the investigation of a 7-year-old girl with empyema and glomerulonephritis whose "immunological" defect was a single complement component (C2) deficiency which prevented her from activating her classical complement pathway. A defect in complement function should be suspected in any patient with severe or recurring pyogenic infections. Investigations of "? immune deficiency" should always include tests to assess the patency of the patient's complement system.

  11. CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

    Directory of Open Access Journals (Sweden)

    Michael P. Pender

    2012-01-01

    Full Text Available CD8+ T-cell deficiency is a feature of many chronic autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, dermatomyositis, primary biliary cirrhosis, primary sclerosing cholangitis, ulcerative colitis, Crohn's disease, psoriasis, vitiligo, bullous pemphigoid, alopecia areata, idiopathic dilated cardiomyopathy, type 1 diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, IgA nephropathy, membranous nephropathy, and pernicious anaemia. It also occurs in healthy blood relatives of patients with autoimmune diseases, suggesting it is genetically determined. Here it is proposed that this CD8+ T-cell deficiency underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of Epstein-Barr virus (EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells which would otherwise die in the target organ by activation-induced apoptosis. Autoimmunity is postulated to evolve in the following steps: (1 CD8+ T-cell deficiency, (2 primary EBV infection, (3 decreased CD8+ T-cell control of EBV, (4 increased EBV load and increased anti-EBV antibodies, (5 EBV infection in the target organ, (6 clonal expansion of EBV-infected autoreactive B cells in the target organ, (7 infiltration of autoreactive T cells into the target organ, and (8 development of ectopic lymphoid follicles in the target organ. It is also proposed that deprivation of sunlight and vitamin D at higher latitudes facilitates the development of autoimmune diseases by aggravating the CD8+ T-cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.

  12. Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.

    Directory of Open Access Journals (Sweden)

    Yulan Qing

    Full Text Available Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs, creating a preleukemic stem cell (PLSC. Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC. Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM, but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus. We studied PLSC linked to thymic lymphomas. In this study, we use MSH2-/- mice as a model to investigate the existence of PLSC and the evolution of PLSC to LIC. Following BM transplantation, we found that MSH2-/- BM cells from young mice are able to fully reconstitute multiple hematopoietic lineages of lethally irradiated wild-type recipients. However, all recipients developed thymic lymphomas within three and four months post transplantation. Transplantation of different fractions of BM cells or thymocytes from young health MSH2-/- mice showed that an HSC enriched fraction always reconstituted hematopoiesis followed by lymphoma development. In addition, lymphomas did not occur in thymectomized recipients of MSH2-/- BM. These results suggest that HSCs with DNA repair defects such as MSH2-/- are PLSCs because they retain hematopoietic function, but also carry an obligate lymphomagenic potential within their T-cell progeny that is dependent on the thymic microenvironment.

  13. A structure-function analysis in patients with prekallikrein deficiency.

    Science.gov (United States)

    Girolami, Antonio; Ferrari, Silvia; Cosi, Elisabetta; Lombardi, Anna Maria

    2017-11-22

    To investigate the structure-function relation in prekallikrein (PK) deficiency. PK is one of the proteins of the contact phase of blood coagulation which at the present time is the object of a revival of interest. All patients with PK deficiency who had been investigated by molecular biology techniques are the object of the present investigation. Details of patients were obtained from personal files and a time-unlimited PubMed search. Only cases with a molecular-biology-based diagnosis were included. Twelve families were included. The total number of missense mutation was 10, together with 3 stop codons and 2 insertions. These mutations involved mainly exons 11 and 14. There were eight proved homozygotes and three compound heterozygotes. In one instance, homozygosity was probable but not proved. In nine cases, the defect was Type I, whereas it was Type II in the remaining three. No bleeding manifestations were present in 11 of the 12 probands. One proband had epistaxis, but she had hypertension. Altogether, four patients had hypertension and one of them had also two myocardial infarctions. Despite the paucity of cases, it was established that the majority of mutations involved the catalytic domain. It is auspicable that future reports of patients with this disorder should include molecular studies. This would certainly contribute to the understanding of the contact phase of blood coagulation.

  14. [A patient with vitamin E deficient, myopathy presenting with amyotrophy].

    Science.gov (United States)

    Osoegawa, M; Ohyagi, Y; Inoue, I; Tsuruta, Y; Iwaki, T; Taniwaki, T; Kira, J

    2001-07-01

    We report a 61-year-old man with vitamin E deficiency, presenting with, myopathy as an only clinical symptom. In 1997, at 59 years of age, he noted mild proxymal-muscle weakness and atrophy in the four extremities, nine years after he received a Billroth II partial gastrectomy for a gastric ulcer. His muscle weakness slowly exacerbated, and he was admitted to our hospital in 1999. On admission, neurological examination confirmed mild proximal-muscle weakness and atrophy in the four extremities. Intelligence, cranial nerves, coordination, sensation and tendon reflexes were all normal. Laboratory examination showed normochromic anemia (Hb 9.9 g/dl, Ht 30.9%, MCV 97.5 fl, MCHC 31.2 pg), hypoproteinemia (5.0 g/dl), and hypocholesterolemia (107 mg/dl). The levels of serum CK, lactate and pyruvate were normal. The serum vitamin E level was markedly reduced (0.17 mg/dl; normal 0.75-1.41). Cerebrospinal fluid was normal. Nerve conduction, sensory evoked potentials (SEP), electromyography (EMG), head CT and electroencephalography (EEG) were all normal. Muscle biopsy from the right deltoid muscle showed both mild myogenic and neurogenic changes. Remarkably, type 1 muscle fiber predominance and granular accumulation of autofluorescent lipofuscin granules in the muscle fibers were found. These pathological findings were compatible with those of vitamin E-deficient myopathy. Thus, he was diagnosed as having vitamin E-deficient myopathy, which was confirmed by apparent effective supplementation of vitamin E. Interestingly, our present case did not show any other neurological manifestations such as deep sensory disturbance, sensory ataxia or polyneuropathy. A long-term workload due to hard physical labor and smoking in our patient may have accelerated oxidative muscle damage, resulting in amyotrophy mainly due to vitamin E deficient myopathy.

  15. Nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand.

    Science.gov (United States)

    Bobba, Samantha; Di Girolamo, Nick; Mills, Richard; Daniell, Mark; Chan, Elsie; Harkin, Damien G; Cronin, Brendan G; Crawford, Geoffrey; McGhee, Charles; Watson, Stephanie

    2017-03-01

    This study aimed to determine the nature and incidence of severe limbal stem cell deficiency (LSCD) in Australia and New Zealand. A 1-year pilot surveillance study with a 1-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit. The study included patients reported by practising ophthalmologists on the Surveillance Unit's database. Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases. Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium and superficial corneal neovascularization or conjunctivalization. On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013 to March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrizing conjunctivitis being the most common (n = 3). This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency; however, because of study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  16. Effects of an induced adenosine deaminase deficiency on T-cell differentiation in the rat

    International Nuclear Information System (INIS)

    Barton, R.W.

    1985-01-01

    Inherited deficiency of the enzyme adenosine deaminase (ADA) has been found in a significant proportion of patients with severe combined immunodeficiency disease and inherited defect generally characterized by a deficiency of both B and T cells. Two questions are central to understanding the pathophysiology of this disease: (1) at what stage or stages in lymphocyte development are the effects of the enzyme deficiency manifested; (2) what are the biochemical mechanisms responsible for the selective pathogenicity of the lymphoid system. We have examined the stage or stages of rat T-cell development in vivo which are affected by an induced adenosine deaminase deficiency using the ADA inhibitors, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and 2'-deoxycoformycin (DCF). In normal rats given daily administration of an ADA inhibitor, cortical thymocytes were markedly depleted; peripheral lymphocytes and pluripotent hemopoietic stem cells (CFU-S) all were relatively unaffected. Since a deficiency of ADA affects lymphocyte development, the regeneration of cortical and medullary thymocytes and their precursors after sublethal irradiation was used as a model of lymphoid development. By Day 5 after irradiation the thymus was reduced to 0.10-0.5% of its normal size; whereas at Days 9 and 14 the thymus was 20-40% and 60-80% regenerated, respectively. When irradiated rats were given daily parenteral injections of the ADA inhibitor plus adenosine or deoxyadenosine, thymus regeneration at Days 9 and 14 was markedly inhibited, whereas the regeneration of thymocyte precursors was essentially unaffected. Thymus regeneration was at least 40-fold lower than in rats given adenosine or deoxyadenosine alone. Virtually identical results were obtained with both ADA inhibitors, EHNA and DCF

  17. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  18. [Vitamin D deficiency and morbimortality in critically ill paediatric patients].

    Science.gov (United States)

    García-Soler, Patricia; Morales-Martínez, Antonio; Rosa-Camacho, Vanessa; Lillo-Muñoz, Juan Antonio; Milano-Manso, Guillermo

    2017-08-01

    To determine the prevalence and risks factors of vitamin D deficiency, as well as its relationship with morbidity and mortality in a PICU. An observational prospective study in a tertiary children's University Hospital PICU conducted in two phases: i: cohorts study, and ii: prevalence study. The study included 340 critically ill children with ages comprising 6 months to 16 years old. Chronic kidney disease, known parathyroid disorders, and vitamin D supplementation. Total 25-hydroxyvitamin D [25(OH)D] was measured in the first 48hours of admission to a PICU. Parathormone, calcium, phosphate, blood gases, blood count, C-reactive protein, and procalcitonin were also analysed. A record was also made of demographic features, characteristics of the episode, and complications during the PICU stay. The overall prevalence rate of vitamin D deficiency was 43.8%, with a mean of 22.28 (95% CI 21.15-23.41) ng/ml. Patients with vitamin D deficiency were older (61 vs 47 months, P=.039), had parents with a higher level of academic studies (36.5% vs 20%, P=.016), were admitted more often in winter and spring, had a higher PRISM-III (6.8 vs 5.1, P=.037), a longer PICU stay (3 vs 2 days, P=.001), and higher morbidity (61.1% vs 30.4%, P<001) than the patients with sufficient levels of 25(OH)D. Patients who died had lower levels of 25(OH)D (14±8.81ng/ml versus 22.53±10.53ng/ml, P=.012). Adjusted OR for morbidity was 5.44 (95%CI; 2.5-11.6). Vitamin D deficiency is frequent in critically ill children, and it is related to both morbidity and mortality, although it remains unclear whether it is a causal relationship or it is simply a marker of severity in different clinical situations. Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics

    DEFF Research Database (Denmark)

    Sturis, Jeppe; Gotfredsen, Carsten F; Rømer, John

    2003-01-01

    (1) Liraglutide is a long-acting GLP-1 derivative, designed for once daily administration in type II diabetic patients. To investigate the effects of liraglutide on glycemic control and beta-cell mass in rat models of beta-cell deficiencies, studies were performed in male Zucker diabetic fatty (Z...... antihyperglycemic effects in rodent models of beta-cell deficiencies, and the in vivo effect of liraglutide on beta-cell mass may in part depend on the metabolic state of the animals....

  20. Ascorbic acid deficiency in patients with lichen planus.

    Science.gov (United States)

    Nicolae, Ilinca; Mitran, Cristina Iulia; Mitran, Madalina Irina; Ene, Corina Daniela; Tampa, Mircea; Georgescu, Simona Roxana

    2017-01-01

    Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin. We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects. The evaluation of all participants included clinical examination and laboratory and imaging tests. Compared to the control group (19.82 mg/dl) the level of ascorbic acid was significantly lower both in patients with CLP (8.47 mg/dl, p = 0.001) and in those with OLP (8.04 mg/dl, p = 0.001). In patients with LP it was found that the deficiency of ascorbic acid increases with age (r = -0.318, p = 0.032). The urinary concentrations of ascorbic acid were significantly lower in patients with LP associated with infections compared to patients with LP without infections. The urinary ascorbic acid level may be a useful parameter in identifying patients with LP who are at risk of developing viral or bacterial infections.

  1. The Relationship between Qi Deficiency, Cancer-related Fatigue and Quality of Life in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Chung-Hua Hsu

    2012-04-01

    Conclusions: The present study showed statistically significant difference in WHO-QOL scores in physical, psychological, and social domains between the groups with and without Qi deficiency as well as the groups with and without CRF. Cancer patients diagnosed with Qi deficiency or CRF have poor QOL. The concept of Qi deficiency in TCM might be applied to cancer health care.

  2. TFEB activation restores migration ability to Tsc1-deficient adult neural stem/progenitor cells.

    Science.gov (United States)

    Magini, Alessandro; Polchi, Alice; Di Meo, Danila; Mariucci, Giuseppina; Sagini, Krizia; De Marco, Federico; Cassano, Tommaso; Giovagnoli, Stefano; Dolcetta, Diego; Emiliani, Carla

    2017-09-01

    Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major pathological feature of TSC is the development of subependymal giant cell astrocytomas (SEGAs) in the brain. Nowadays, it is thought that SEGAs could be a consequence of aberrant aggregation and migration of neural stem/progenitor cells (NSPCs). Therefore, reactivation of cell migration of NSPCs might be the crucial step for the treatment of patients. In order to identify potential in vitro targets activating migration, we generated Tsc1-deficient NSPCs. These cells summarize most of the biochemical and morphological characteristics of TSC neural cells, such as the mTORC1 activation, the formation of abnormally enlarged astrocytes-like cells, the reduction of autophagy flux and the impairment of cell migration. Moreover, nuclear translocation, namely activation of the transcription factor EB (TFEB) was markedly impaired. Herein, we show that compounds such as everolimus, ionomycin and curcumin, which directly or indirectly stimulate TFEB nuclear translocation, restore Tsc1-deficient NSPC migration. Our data suggest that reduction of TFEB activation, caused by mTORC1 hyperactivation, contributes to the migration deficit characterizing Tsc1-deficient NSPCs. The present work highlights TFEB as a druggable protein target for SEGAs therapy, which can be additionally or alternatively exploited for the mTORC1-directed inhibitory approach. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers.

    Science.gov (United States)

    Aguilar, Claire; Lenoir, Christelle; Lambert, Nathalie; Bègue, Bernadette; Brousse, Nicole; Canioni, Danielle; Berrebi, Dominique; Roy, Maryline; Gérart, Stéphane; Chapel, Helen; Schwerd, Tobias; Siproudhis, Laurent; Schäppi, Michela; Al-Ahmari, Ali; Mori, Masaaki; Yamaide, Akiko; Galicier, Lionel; Neven, Bénédicte; Routes, John; Uhlig, Holm H; Koletzko, Sibylle; Patel, Smita; Kanegane, Hirokazu; Picard, Capucine; Fischer, Alain; Bensussan, Nadine Cerf; Ruemmele, Frank; Hugot, Jean-Pierre; Latour, Sylvain

    2014-11-01

    Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients. We characterize the IBD affecting a large cohort of patients with mutations in XIAP and examine the possible pathophysiologic mechanisms. We performed a phenotypical and histologic analysis of the IBD affecting 17 patients with hemizygous mutations in XIAP, including 3 patients identified by screening 83 patients with pediatric-onset IBD. The X chromosome inactivation was analyzed in female carriers of heterozygous XIAP mutations, including 2 adults with IBD. The functional consequences of XIAP deficiency were analyzed. Clinical presentation and histology of IBD in patients with XIAP deficiency overlapped with those of patients with Crohn disease. The age at onset was variable (from 3 months to 41 years), and IBD was severe and difficult to treat. In 2 patients hematopoietic stem cell transplantation fully restored intestinal homeostasis. Monocytes of patients had impaired NOD2-mediated IL-8 and monocyte chemoattractant protein 1 (MCP-1) production, as well as IL-10, in response to NOD2 and Toll-like receptor 2/4 costimulation. Nucleotide binding and oligomerization domain containing 1 (NOD1)-mediated IL-6 and IL-8 production was defective in fibroblasts from XIAP-deficient patients. The 2 heterozygous female carriers of XIAP mutations with IBD displayed abnormal expression of the XIAP mutated allele, resulting in impaired activation of the NOD2 pathway. IBD in patients with XIAP deficiency is similar to Crohn disease and is associated with defective NOD2 function in monocytes. Importantly, we report that it is not restricted to male patients

  4. Deficient Pain Modulation in Patients with Chronic Hemiplegic Shoulder Pain.

    Science.gov (United States)

    Kashi, Yafit; Ratmansky, Motti; Defrin, Ruth

    2017-11-14

    Hemiplegic shoulder pain (HSP) following stroke significantly affects the individual's function and quality of life. The mechanism of HSP is not clearly understood; hence, it is unclear why HSP resolves spontaneously or following routine care in some patients, while in others it becomes persistent. The aim was therefore to study whether HSP is associated with deficient pain modulation. Thirty post-stroke patients-16 with HSP and 14 without HSP-and 20 matched controls participated. Pain adaptation and conditioned pain modulation (CPM) were measured as indicators of pain modulation, in the affected (hemiplegic) and contralateral shoulder as well as in the affected shin among post-stroke patients, and in comparable body regions among controls. Post-stroke patients also underwent functional and physical evaluation of the shoulder. Pain adaptation was absent among HSP patients, in both the painful shoulder and the affected shin, but existed in the 2 control groups. In addition, the affected shoulder and shin among the HSP group had reduced thermal sensibility compared to the contralateral regions. CPM was similar across groups. Shoulder functional status and physical status were similar for the 2 post-stroke groups. The results suggest that HSP is associated with a lack of pain adaptation, characteristic not only of the painful shoulder but also of the affected side. Although we cannot determine whether lack of pain adaptation precedes the HSP or results from it, interventions that enhance descending pain inhibition may improve management and prevent HSP chronification. © 2017 World Institute of Pain.

  5. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  6. Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

    Directory of Open Access Journals (Sweden)

    Megumi Bessho

    Full Text Available Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD, i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

  7. Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1).

    Science.gov (United States)

    Schubert, Desirée; Klein, Marie-Christine; Hassdenteufel, Sarah; Caballero-Oteyza, Andrés; Yang, Linlin; Proietti, Michele; Bulashevska, Alla; Kemming, Janine; Kühn, Johannes; Winzer, Sandra; Rusch, Stephan; Fliegauf, Manfred; Schäffer, Alejandro A; Pfeffer, Stefan; Geiger, Roger; Cavalié, Adolfo; Cao, Hongzhi; Yang, Fang; Li, Yong; Rizzi, Marta; Eibel, Hermann; Kobbe, Robin; Marks, Amy L; Peppers, Brian P; Hostoffer, Robert W; Puck, Jennifer M; Zimmermann, Richard; Grimbacher, Bodo

    2017-08-04

    Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation. We identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs. Whole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B-cell differentiation and survival. We investigated 2 families with patients with hypogammaglobulinemia, severe recurrent respiratory tract infections, and normal peripheral B- and T-cell subpopulations. On in vitro stimulation, B cells showed an intrinsic deficiency to develop into PCs. Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in cotranslational protein translocation, and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response in multiple myeloma cell lines. We describe a monogenic defect leading to a specific PC deficiency in human subjects, expanding our knowledge about the pathogenesis of antibody deficiencies. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  8. Vitamin D deficiency in type 2 diabetic patients with hypogonadism.

    Science.gov (United States)

    Bellastella, Giuseppe; Maiorino, Maria Ida; Olita, Laura; Capuano, Annalisa; Rafaniello, Concetta; Giugliano, Dario; Esposito, Katherine

    2014-02-01

    Both type 2 diabetes and secondary hypogonadism may be associated with low vitamin D levels. The aim of this study was to evaluate 25-hydroxyvitamin D (25(OH)D) concentrations in type 2 diabetic males with and without hypogonadism. We performed a case-control study among 122 male adults with type 2 diabetes, 51 with associated hypogonadism (Group 1) and 71 with normal gonadal function (Group 2). One hundred age-matched nondiabetic males with normal gonadal function served as a control group. Levels of 25(OH)D were assessed by a chemiluminescent immunoassay in all patients. Morning testosterone, pituitary, thyroid, parathyroid hormones, fasting glucose, and hemoglobin A1c were also evaluated. The overall diabetic population showed a mean 25(OH)D concentration (22.3 ± 6.09 ng/mL) significantly lower than the control group (34.3 ± 7.2, P hypogonadism as compared with the 9 patients with hypergonadotropic hypogonadism (19.4 ± 7.06 vs. 23.8 ± 6.11 ng/mL, P hypogonadism present lower 25(OH)D concentration and higher prevalence of vitamin D deficiency, compared with patients without hypogonadism. The finding that 25(OH)D concentrations were similar between type 2 diabetic patients with hypergonadotropic hypogonadism and those with normal gonadal function deserves further study. © 2013 International Society for Sexual Medicine.

  9. Vitamin D deficiency in children and adolescents submitted to hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Denise Johnsson Campos

    2014-04-01

    Full Text Available Background: Sub-optimal levels of vitamin D have been found to be highly prevalent in all age groups, with epidemiologic studies demonstrating a link between vitamin D deficiency and disease susceptibility, such as infection and cancer, and mortality rates. In adult transplant patients, it has been suggested that the immunomodulatory properties of vitamin D may have an important role in the prevention and treatment of graft-versus-host disease. Objective: The objective of this study was to assess serum 25-hydroxyvitamin D levels of children and adolescents submitted to allogeneic hematopoietic stem cell transplantation. Methods: Serum 25-hydroxyvitamin D levels of 66 patients, aged 4-20 years, were assessed at three stages: before hospitalization for hematopoietic stem cell transplantation and at 30 and 180 days after hematopoietic stem cell transplantation. The control group consisted of 25 healthy children. Results: At the pre-hematopoietic stem cell transplantation stage, patients had lower levels of 25-hydroxyvitamin D compared to controls (25.7 ± 12.3 ng/mL vs. 31.9 ± 9.9 ng/mL; p-value = 0.01, and a higher prevalence of 25-hydroxyvitamin D deficiency (32% vs. 8%; p-value = 0.01. Prevalence increased significantly after hematopoietic stem cell transplantation (p-value = 0.01 with half of the patients having vitamin D deficiency at 180 days after transplantation. At this stage, mean serum 25-hydroxyvitamin D levels were 20.9 ± 10.9 ng/mL, a significant decline in relation to baseline (p-value = 0.01. No correlation was found between 25-hydroxyvitamin D levels and vitamin D intake, graft-versus-host disease, corticoid use or survival rates. Conclusion: Low levels of 25-hydroxyvitamin D were detected even before hematopoietic stem cell transplantation and were significantly lower at 180 days after hematopoietic stem cell transplantation, thus recommending vitamin D supplementation for children and adolescents submitted to hematopoietic stem

  10. [Pharyngeal ulcer in patients with acquired immune deficiency syndrome].

    Science.gov (United States)

    Fang, Gaoli; Zhang, Luo; Wang, Chengshuo; Xiao, Jiang; Fu, Qian; Zhao, Hongxin

    2014-02-01

    To understand the high incidence of pharyngeal ulcer in patients with acquired immune deficiency syndrome (AIDS). By analyzing the clinical features in AIDS patients with pharyngeal ulcer, this study provided reference for clinicians. Twenty AIDS patients with pharyngeal ulcer were retrospectively analysed to explore its clinical features and mechanism, and to explore the feasible therapeutic methods. The patients generally had severe sore throat and dysphagia for 7 days to 8 months, resulting in significant weight loss. Common therapeutical method does not work. The ulcers developed mainly at vestibule of pharynx (10 cases), tonsil (3 cases), epiglottis (3 cases) and pyriform sinus (2 cases). Ulcer types included major aphthous ulcer (MaAU, 14 cases), fungal ulcer (2 cases), herpes zoster (1 case), ulcer secondary to drug eruption(1 case ), and lymphoma(2 cases). The disease course was long with CD4(+) T lymphocytes decreased significantly. Treatment was given with highly active antiretroviral therapy (HARRT), regulation of immune function, analgesic, anti-inflammatory and anti fungal. Treatment lasted from 2 weeks to 3 months, ulcer healed in 13 cases; 1 patient lost to follow-up, 6 patients dead. The manifestation of pharyngeal ulcer in AIDS patients has its particularity. It is often associated with a variety of opportunistic infection and tumors. Local treatment is preferred. HAART therapy and systemic comprehensive treatment play more important and effective role. Pharyngeal ulcer persists for a long time, complicated with fever, diarrhea and other symptoms. The history of blood transfusion, injection drug use or unsafe sexual behavior may predict HIV infection.

  11. Changes in red blood cell membrane structure in G6PD deficiency: an atomic force microscopy study.

    Science.gov (United States)

    Tang, Jia; Jiang, Chengrui; Xiao, Xiao; Fang, Zishui; Li, Lei; Han, Luhao; Mei, Anqi; Feng, Yi; Guo, Yibin; Li, Hongyi; Jiang, Weiying

    2015-04-15

    Glucose-6-phosphate dehydrogenase deficiency affects over 400 million people worldwide. The hemolytic anemia in G6PD deficiency is usually triggered by oxidative stress, but the mechanism remains uncertain. We have used atomic force microscopy for studying changes in red blood cell membrane and providing new insights on the mechanism. G6PD activity assay and molecular genetic tests were used for molecular diagnosis. AFM was used to investigate alterations in the ultrastructure of G6PD deficient RBC membranes, the influence of different primaquine concentrations, and the protective effects of vitamin C. Nine variants were identified from 33 G6PD deficient individuals. AFM imaging and quantitative analysis showed that G6PD deficient erythrocytes became heterogeneous and roughness measurements of erythrocyte membranes are increased. G6PD enzyme activity and different mutations may relate with roughness parameters. Furthermore, primaquine induces an increased roughness and height of erythrocyte membrane. Meanwhile, primaquine induces damages to erythrocytes which could be prevented by vitamin C treatment in normal RBCs but not in G6PD deficient erythrocytes. Our research may give valuable information about the status of G6PD deficient patients and explore the mechanism of hemolytic anemia. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Study on changes of serum ferritin (SF), folic acid (FA) and vitamin B12 levels after transfusion of preserved red cells (PRC) in patients with iron deficiency anemia (IDA)

    International Nuclear Information System (INIS)

    Liu Hongsu; Li Xinhua; Li Keqin

    2008-01-01

    Objective: To explore the changes of serum SF, FA and VitB 12 levels after transfusion of preserved red cells in patients with IDA. Methods: Serum SF, FA and VitB 12 levels (with RIA) were detected both before and after transfusion of preserved red cells in 32 patients with IDA as well as in 35 controls. Results: Before transfusion of preserved red cells, the serum SF levels were significantly lower than those in controls (P 12 levels were significantly higher (P 12 were not much different from those in the controls. Conclusion: Transfusion of preserved red cells proves to be very useful. (authors)

  13. PTEN deficiency reprogrammes human neural stem cells towards a glioblastoma stem cell-like phenotype

    Science.gov (United States)

    Duan, Shunlei; Yuan, Guohong; Liu, Xiaomeng; Ren, Ruotong; Li, Jingyi; Zhang, Weizhou; Wu, Jun; Xu, Xiuling; Fu, Lina; Li, Ying; Yang, Jiping; Zhang, Weiqi; Bai, Ruijun; Yi, Fei; Suzuki, Keiichiro; Gao, Hua; Esteban, Concepcion Rodriguez; Zhang, Chuanbao; Belmonte, Juan Carlos Izpisua; Chen, Zhiguo; Wang, Xiaomin; Jiang, Tao; Qu, Jing; Tang, Fuchou; Liu, Guang-Hui

    2015-01-01

    PTEN is a tumour suppressor frequently mutated in many types of cancers. Here we show that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells (NSCs), but not mesenchymal stem cells. PTEN-deficient NSCs display neoplasm-associated metabolic and gene expression profiles and generate intracranial tumours in immunodeficient mice. PTEN is localized to the nucleus in NSCs, binds to the PAX7 promoter through association with cAMP responsive element binding protein 1 (CREB)/CREB binding protein (CBP) and inhibits PAX7 transcription. PTEN deficiency leads to the upregulation of PAX7, which in turn promotes oncogenic transformation of NSCs and instates ‘aggressiveness' in human glioblastoma stem cells. In a large clinical database, we find increased PAX7 levels in PTEN-deficient glioblastoma. Furthermore, we identify that mitomycin C selectively triggers apoptosis in NSCs with PTEN deficiency. Together, we uncover a potential mechanism of how PTEN safeguards NSCs, and establish a cellular platform to identify factors involved in NSC transformation, potentially permitting personalized treatment of glioblastoma. PMID:26632666

  14. Protein-C deficiency presenting as pulmonary embolism and myocardial infarction in the same patient.

    Science.gov (United States)

    Maqbool, Syed; Rastogi, Vishal; Seth, Ashok; Singh, Satbir; Kumar, Vijay; Mustaqueem, Arif

    2013-10-01

    Plasma protein-C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis occurring as a result of congenital protein-C deficiency is still controversial. We describe a young patient with heterozygous protein-C deficiency who experienced both pulmonary embolism as well as myocardial infarction due to thrombotic occlusion without underlying major risk factors. Acute myocardial infarction in young without underlying major risk factors may be evaluated for protein c deficiency.

  15. Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients

    DEFF Research Database (Denmark)

    Møller, Jens; Laursen, Torben; Mindeholm, Linda

    1994-01-01

    Abstract OBJECTIVE: GH-deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and in GH...... deficient patients in two separate studies. DESIGN: Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl-L-alpha-phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril......) at the beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m2 intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed. PATIENTS: Eight normal subjects and 7 GH deficient patients...

  16. Helicobacter pylori infection in patients with selective immunoglobulin a deficiency.

    Science.gov (United States)

    Magen, E; Waitman, D-A; Goldstein, N; Schlesinger, M; Dickstein, Y; Kahan, N R

    2016-06-01

    Selective immunoglobulin A (IgA) deficiency (IgAD) is the most common primary immunodeficiency in the western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori-infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729) who had undergone serum total IgA measurements during 2004-14 for any reason at Leumit Healthcare Services (Israel) and had serum total IgA < 0·07 g/l. The control group was comprised of a random sample of remaining patients with a case-control ratio of 10 controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes. The case group included 347 subjects and the control group 3470 subjects. There were no significant differences in the prevalence of patients with dyspepsia [84 (24·2%) versus 821 (23·6%) for cases and controls, respectively]. Additionally, there was no difference in a proportion of dyspeptic H. pylori-positive subjects [59 (17·1%) versus 524 (15·1%)] between the case and control groups. Only 59 (17%) among the 347 IgAD patients underwent gastroscopy. A significantly larger proportion of case subjects experienced several forms of gastritis [13 (61·9%) versus 38 (21·6%), P < 0·001), duodenal ulcers [seven (33·3%) versus 19 (10·8%); P = 0·01] and nodular lymphoid hyperplasia (NLH) [two (9·5%) versus none; P = 0·011]. IgAD is not associated with increased prevalence of H. pylori-associated dyspepsia; nevertheless, H. pylori-infected dyspeptic IgAD subjects experience more EGD-proved gastritis, duodenal ulcers and NLH. © 2016 British Society for Immunology.

  17. Zinc Status in Iron Deficient Anaemic Patients in Sudan

    NARCIS (Netherlands)

    Yagob Mohamed, T.I.; Bode, P.; van de Wiel, A.; Ismail, Fadwa; Wolterbeek, H.T.

    2017-01-01

    Iron deficiency anaemia is a major health problem worldwide, but may be complicated in underdeveloped nations by deficiencies of other micronutrients with consequences for adequate treatment. The World Health Organization (WHO) estimates that 2 billion people – over 30% of the world’s population –

  18. Short-term outcome of Boston Type 1 keratoprosthesis for bilateral limbal stem cell deficiency

    Directory of Open Access Journals (Sweden)

    Sayan Basu

    2012-01-01

    Full Text Available This study reports the short-term functional and anatomical outcome of Boston Type 1 keratoprosthesis (Boston Kpro implantation for bilateral limbal stem cell deficiency (LCSD. Retrospective analysis was done on eight eyes of eight patients who underwent Boston Kpro implantation between July 2009 and October 2009. The best corrected visual acuity (BCVA and slit-lamp biomicroscopy findings were assessed at 1, 3 and 6 months postoperatively. All eight eyes retained the prosthesis. BCVA of 20/40 or better was achieved in 8, 6, and 5 eyes at 1, 3, and 6 months, respectively, postoperatively. One patient each developed epithelial defect, sterile stromal melt and fungal keratitis in the late postoperative period associated with antecedent loss of the soft contact lens from the eye. Boston Kpro has good short-term visual and anatomical outcome in patients with bilateral LSCD, provided compliance with postoperative care can be ensured.

  19. The association of pagophagia with Helicobacter pylori infection in patients with iron-deficiency anemia.

    Science.gov (United States)

    Asma, Suheyl; Boga, Can; Ozdogu, Hakan; Serin, Ender

    2009-07-01

    This study aimed to determine the relationship between pagophagia (compulsive ice eating) and H. pylori infection in patients with iron-deficiency anemia. We identified H. pylori infection using the (13)C-urea breath test in 45 patients with iron-deficiency anemia (group 1) and 55 patients with iron-deficiency anemia and pagophagia (group 2). Subgroups for testing oral intestinal iron absorption were randomly assigned from both groups. These subgroups consisted of (a) 10 patients with iron-deficiency anemia, (b) 10 patients with iron-deficiency anemia and pagophagia, (c) 10 patients with iron-deficiency anemia, pagophagia, and H. pylori infection before the eradication of H. pylori and (d) subgroup c after eradication therapy. There was no difference in the rate of H. pylori infection in the iron-deficiency anemia groups, with or without pagophagia. Furthermore, oral intestinal iron absorption was not influenced by pagophagia and/or H. pylori infection. Pagophagia did not increase the risk of H. pylori infection in patients with iron-deficiency anemia. Pagophagia and H. pylori infection do not synergistically affect the development of intestinal iron absorption abnormalities.

  20. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2011-01-01

    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  1. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

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    Mehdi Shakibaei

    Full Text Available OBJECTIVE: Treatment of colorectal cancer (CRC remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin in context of DNA mismatch repair (MMR status and CSC activity in 3D cultures of CRC cells. METHODS: High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3 and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. RESULTS: Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. CONCLUSION: Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract.

  2. Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

    Science.gov (United States)

    Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

    2014-01-01

    Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).

  3. Compensatory T cell responses in IRG-deficient mice prevent sustained Chlamydia trachomatis infections.

    Directory of Open Access Journals (Sweden)

    Jörn Coers

    2011-06-01

    Full Text Available The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States. In women C. trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease and sterility. In contrast to natural infections in humans, experimentally induced infections with C. trachomatis in mice are rapidly cleared. The cytokine interferon-γ (IFNγ plays a critical role in the clearance of C. trachomatis infections in mice. Because IFNγ induces an antimicrobial defense system in mice but not in humans that is composed of a large family of Immunity Related GTPases (IRGs, we questioned whether mice deficient in IRG immunity would develop persistent infections with C. trachomatis as observed in human patients. We found that IRG-deficient Irgm1/m3((-/- mice transiently develop high bacterial burden post intrauterine infection, but subsequently clear the infection more efficiently than wildtype mice. We show that the delayed but highly effective clearance of intrauterine C. trachomatis infections in Irgm1/m3((-/- mice is dependent on an exacerbated CD4(+ T cell response. These findings indicate that the absence of the predominant murine innate effector mechanism restricting C. trachomatis growth inside epithelial cells results in a compensatory adaptive immune response, which is at least in part driven by CD4(+ T cells and prevents the establishment of a persistent infection in mice.

  4. [Vitamin D deficiency in a Spanish cohort of patients with chronic kidney disease].

    Science.gov (United States)

    Yuste, Claudia; García De Vinuesa, Soledad; Goicoechea, Marian; Barraca, Daniel; Panizo, Nayara; Quiroga, Borja; Luño, Jose

    2013-10-19

    Vitamin D (25-OH-D3) deficiency is an emerging global health problem. Chronic kidney disease (CKD) patients have a higher risk of this deficiency. We aimed to determine the prevalence of 25-OH-D3 deficiency in a cohort of CKD patients in an urban area of Spain and its relationship with cardiovascular disease (CVD). We evaluated the prevalence of 25-OH-D3 deficiency in 751 incident patients referred to our outpatient clinic (male gender 59.3%, mean age 67.2 [± 15] years, mean GFR (MDRD-4) 47.9 ± 25.5 ml/min/1.73 m(2)) with different stages of CKD. We excluded end stage renal disease patients and with kidney transplant. Clinical data and biochemical parameters related to bone and mineral metabolism were recorded. Levels of 25-OH-D3D3 levels were 17.06 [± 12.93] ng/ml. Only 10% of our patients had adequate 25-OH-D3 levels (>30 ng/ml) and 51% showed deficient levels. 25-OH-D3 deficiency worsened with the progression of CKD (PD3 deficiency. 25-OH-D3 deficiency was inversely associated with serum PTH (P=.02), and directly associated with serum calcium (PD3 levels (P=.038). 25-OH-D3 deficiency has a high prevalence in CKD patients, and the severity increases with the progression of kidney disease. Elderly, women and diabetic patients have a higher risk of 25-OH-D3 deficiency. 25-OH-D3 deficiency was related to higher levels of PTH and lower serum calcium. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  5. The Value of Erythrocyte Indices and Red Cell Volume Distribution Width in Differential Diagnosis of Iron Deficiency Anemia and Anemia of Chronic Disease

    OpenAIRE

    Abdullah Altıntaş

    2007-01-01

    Iron deficiency anemia (IDA) and anemia of chronic disease are the most commonly confused anemias. We investigate the diagnostic value of erythrocyte indices, red cell volume distribution width, and serum ferritin levels to make differential diagnosis of anemia in controls and anemic patients.Iron deficiency anemia (44 patients), anemia of chronic disease (41), IDA with anemia of chronic disease (17) and control (50) groups were compared. We performed serum ferritin, CBC, and sedimentation ra...

  6. Bilateral Lung Transplantation in a Patient with Humoral Immune Deficiency: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jocelyn R. Farmer

    2014-01-01

    Full Text Available Humoral immune deficiencies have been associated with noninfectious disease complications including autoimmune cytopenias and pulmonary disease. Herein we present a patient who underwent splenectomy for autoimmune cytopenias and subsequently was diagnosed with humoral immune deficiency in the context of recurrent infections. Immunoglobulin analysis prior to initiation of intravenous immunoglobulin (IVIG therapy was notable for low age-matched serum levels of IgA (11 mg/dL, IgG2 (14 mg/L, and IgG4 (5 mg/L with a preserved total level of IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+ stage. Selective screening for known primary immune deficiency-causing genetic defects was negative. The disease course was uniquely complicated by the development of pulmonary arteriovenous malformations (AVMs, ultimately requiring bilateral lung transplantation in 2012. This is a patient with humoral immune deficiency that became apparent only after splenectomy, which argues for routine immunologic evaluation prior to vaccination and splenectomy. Lung transplantation is a rare therapeutic endpoint and to our knowledge has never before been described in a patient with humoral immune deficiency for the indication of pulmonary AVMs.

  7. B-lymphocyte subpopulations in patients with selective IgA deficiency.

    Science.gov (United States)

    Nechvatalova, Jana; Pikulova, Zdenka; Stikarovska, Dagmar; Pesak, Sava; Vlkova, Marcela; Litzman, Jiri

    2012-06-01

    Selective deficiency IgA (IgAD) is the most common primary abnormality of immunoglobulin production with unknown pathophysiology. It is genetically related to common variable immunodeficiency (CVID), where besides IgA also IgG and frequently IgM serum levels are decreased. In this study we focused on determination of B-lymphocyte developmental stages and searching for similarities between CVID and IgAD. Using flow cytometry we determined major lymphocyte subpopulations and B-lymphocyte subsets: naïve (CD27(-)IgD(+)), marginal zone cells (CD27(+)IgD(+)), class-switched memory cells (CD27(+)IgD(-)), "double-negative" B cells (CD27(-)IgD(-)), transitional cells (IgM(++)CD38(++)), plasmablasts (CD38(+++)IgM(+) or IgM(-)), and CD21(low)CD38(low) cells in 80 patients with IgAD, 48 patients with CVID, and 80 control persons. Compared to healthy controls, a decrease in the absolute number and frequency of CD4+ cells (both < 0.001) was observed in IgAD patients. A decrease in the frequency of switched memory cells (P < 0.001), transitional cells (P = 0.035) as well as plasmablasts (P < 0.001) and an increase in the CD21(low)CD38(low) subset (P = 0.007) was observed in IgAD patients compared to control persons. No significant differences were observed in the remaining B-cell developmental subsets. A decrease in CD27(+)IgD(-) (<0.4% of peripheral blood lymphocytes), frequently observed in CVID patients and also previously reported in IgAD, was found in only five patients (6%) with IgAD, two of them being first-degree relatives of CVID patients. Our results show a decrease of terminally differentiated B-lymphocyte subsets in patients with IgAD, similar as previously found in patients with CVID, but these results are less expressed than in CVID patients.

  8. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Carl Johan Drott

    Full Text Available Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1, that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.

  9. Leaky RAG Deficiency in Adult Patients with Impaired Antibody Production against Bacterial Polysaccharide Antigens.

    Directory of Open Access Journals (Sweden)

    Christoph B Geier

    Full Text Available Loss of function mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause a T-B-NK+ type of severe combined immunodeficiency. In addition identification of hypomorphic mutations in RAG1 and RAG2 has led to an expansion of the spectrum of disease to include Omenn syndrome, early onset autoimmunity, granuloma, chronic cytomegalovirus- or EBV-infection with expansion of gamma/delta T-cells, idiophatic CD4 lymphopenia and a phenotype resembling common variable immunodeficiency. Herein we describe a novel presentation of leaky RAG1 and RAG2 deficiency in two unrelated adult patients with impaired antibody production against bacterial polysaccharide antigens. Clinical manifestation included recurrent pneumonia, sinusitis, otitis media and in one patient recurrent cutaneous vasculitis. Both patients harbored a combination of a null mutation on one allele with a novel hypomorphic RAG1/2 mutation on the other allele. One of these novel mutations affected the start codon of RAG1 and resulted in an aberrant gene and protein expression. The second novel RAG2 mutation leads to a truncated RAG2 protein, lacking the C-terminus with intact core RAG2 and reduced VDJ recombination capacity as previously described in a mouse model. Both patients presented with severely decreased numbers of naïve CD4+ T cells and defective T independent IgG responses to bacterial polysaccharide antigens, while T cell-dependent IgG antibody formation e.g. after tetanus or TBEV vaccination was intact. In conclusion, hypomorphic mutations in genes responsible for SCID should be considered in adults with predominantly antibody deficiency.

  10. Vitamin D deficiency is common in psychogeriatric patients, independent of diagnosis.

    Science.gov (United States)

    Grønli, Ole; Kvamme, Jan Magnus; Jorde, Rolf; Wynn, Rolf

    2014-05-08

    Previous studies have found an association between psychiatric disorders and vitamin D deficiency, but most studies have focused on depression. This study aimed to establish the prevalence of vitamin D deficiency in elderly patients with a wider range of psychiatric diagnoses. The study included elderly patients (>64 years) referred to a psychiatric hospital in Northern Norway and a control group from a population survey in the same area. An assessment of psychiatric and cognitive symptoms and diagnoses was conducted using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for Depression in Dementia, the Mini Mental State Examination, the Clockdrawing Test, and the Mini International Neuropsychiatric Interview (MINI+), as well as clinical interviews and a review of medical records. The patients' mean level of 25-hydroxyvitamin D (25(OH)D) and the prevalence of vitamin D deficiency were compared with those of a control group, and a comparison of vitamin D deficiency across different diagnostic groups was also made. Vitamin D deficiency was defined as 25(OH)D deficiency was found in the patient group compared with the control group (71.6% and 20.0%, respectively; p deficiency was still associated with patient status (OR: 12.95, CI (95%): 6.03-27.83, p deficiency were found between patients with different categories of psychiatric diagnoses, such as depression, bipolar disorders, psychosis, and dementia. Vitamin D deficiency is very common among psychogeriatric patients, independent of diagnostic category. Even though the role of vitamin D in psychiatric disorders is still not clear, we suggest screening for vitamin D deficiency in this patient group due to the importance of vitamin D for overall health.

  11. Iron deficiency anemia and megaloblastic anemia in obese patients

    OpenAIRE

    Arshad Mahmoud; Jaberian Sara; Pazouki Abdolreza; Riazi Sajedeh; Rangraz Maryam Aghababa; Mokhber Somayyeh

    2017-01-01

    Background. The association between obesity and different types of anemia remained uncertain. The present study aimed to assess the relation between obesity parameters and the occurrence of iron deficiency anemia and also megaloblastic anemia among Iranian population.

  12. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia.

    Science.gov (United States)

    Horn, Julia; Schlesier, Michael; Warnatz, Klaus; Prasse, Antje; Superti-Furga, Andrea; Peter, Hans-Hartmut; Salzer, Ulrich

    2010-09-01

    Cartilage hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene. Although its most constant feature is metaphyseal dysplasia with short stature, CHH is associated with extraskeletal defects such as thin hair, anemia, immunodeficiency, and increased incidence of lymphomas. The spectrum of immunologic phenotypes in CHH translates into clinical severity. Whereas T-cell deficiency may remain subclinical or may result in severe combined immunodeficiency or Omenn syndrome, humoral immunodeficiency has only rarely been noted in these patients. Here we report the diagnosis of CHH in a woman who presented with severe short stature and a full-blown antibody deficiency, clinically resembling common variable immunodeficiency. Sequencing of the RMRP gene revealed compound heterozygosity for two novel mutations (g.68_69delinsTT and g.76C>T). Despite the late onset of immunodeficiency in the patient, its clinical course was severe, and the patient died 3 years after the first diagnosis. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  13. Iron Deficiency and Anemia Predict Mortality in Patients with Tuberculosis123

    Science.gov (United States)

    Isanaka, Sheila; Mugusi, Ferdinand; Urassa, Willy; Willett, Walter C.; Bosch, Ronald J.; Villamor, Eduardo; Spiegelman, Donna; Duggan, Christopher; Fawzi, Wafaie W.

    2012-01-01

    Many studies have documented a high prevalence of anemia among tuberculosis (TB) patients and anemia at TB diagnosis has been associated with an increased risk of death. However, little is known about the factors contributing to the development of TB-associated anemia and their importance in TB disease progression. Data from a randomized clinical trial of micronutrient supplementation in patients with pulmonary TB in Tanzania were analyzed. Repeated measures of anemia with iron deficiency, anemia without iron deficiency, and iron deficiency without anemia were assessed as risk factors for treatment failure, TB recurrence, and mortality. The prevalence of anemia (hemoglobin iron deficiency (mean corpuscular volume , 80 fL). We found no evidence of an association between anemia (with or without iron deficiency) or iron deficiency without anemia at baseline and the risk of treatment failure at 1 mo after initiation. Anemia without iron deficiency was associated with an independent, 4-fold increased risk of TB recurrence [adjusted RR = 4.10 (95% CI = 1.88, 8.91); P Iron deficiency and anemia (with and without iron deficiency) were associated with a 2- to nearly 3-fold independent increase in the risk of death [adjusted RR for iron deficiency without anemia = 2.89 (95% CI = 1.53, 5.47); P = 0.001; anemia without iron deficiency = 2.72 (95% CI = 1.50, 4.93); P = 0.001; iron deficiency anemia = 2.13 (95% CI = 1.10, 4.11); P = 0.02]. Efforts to identify and address the conditions contributing to TB-associated anemia, including iron deficiency, could play an important role in reducing morbidity and mortality in areas heavily affected by TB. PMID:22190024

  14. Induced Pluripotent Stem Cell Models of Progranulin-Deficient Frontotemporal Dementia Uncover Specific Reversible Neuronal Defects

    Directory of Open Access Journals (Sweden)

    Sandra Almeida

    2012-10-01

    Full Text Available The pathogenic mechanisms of frontotemporal dementia (FTD remain poorly understood. Here we generated multiple induced pluripotent stem cell lines from a control subject, a patient with sporadic FTD, and an FTD patient with a novel heterozygous GRN mutation (progranulin [PGRN] S116X. In neurons and microglia differentiated from PGRN S116X induced pluripotent stem cells, the levels of intracellular and secreted PGRN were reduced, establishing patient-specific cellular models of PGRN haploinsufficiency. Through a systematic screen of inducers of cellular stress, we found that PGRN S116X neurons, but not sporadic FTD neurons, exhibited increased sensitivity to staurosporine and other kinase inhibitors. Moreover, the serine/threonine kinase S6K2, a component of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways, was specifically downregulated in PGRN S116X neurons. Both increased sensitivity to kinase inhibitors and reduced S6K2 were rescued by PGRN expression. Our findings identify cell-autonomous, reversible defects in patient neurons with PGRN deficiency, and provide a compelling model for studying PGRN-dependent pathogenic mechanisms and testing potential therapies.

  15. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

    Science.gov (United States)

    Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

    2014-02-01

    The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

  16. Infectious Keratitis in Limbal Stem Cell Deficiency: Stevens-Johnson Syndrome Versus Chemical Burn.

    Science.gov (United States)

    Kang, Byeong Soo; Kim, Mee Kum; Wee, Won Ryang; Oh, Joo Youn

    2016-01-01

    To investigate the incidence, clinical and microbiological characteristics, risk factors, and therapeutic outcome of infectious keratitis in patients with limbal stem cell deficiency (LSCD) related to Stevens-Johnson syndrome (SJS) and corneal chemical burn. Medical records of 90 eyes of 59 patients who were diagnosed with LSCD resulting from SJS (52 eyes of 29 patients) or corneal chemical burn (38 eyes of 30 patients) were reviewed. Infectious keratitis developed in 35% of LSCD patients with SJS (18 eyes, 14 patients) and in 18% of those with chemical burn (7 eyes, 7 patients). The development of infectious keratitis in SJS was significantly associated with the severity of chronic ocular surface complications in the cornea, conjunctiva, and eyelids and with the use of topical corticosteroids during the disease course. All cases of infectious keratitis following chemical burn occurred in patients with grade III or IV burn by Roper-Hall classification. Approximately 83% of culture-proven cases of infectious keratitis were bacterial infection, most of which (80%) were caused by Gram-positive bacteria. For resolution of infection, 17 eyes (68%) received surgery in addition to medical treatment, whereas 8 eyes (32%) received medical treatment alone. After infection resolution, the final visual acuity was decreased in 10 eyes (40%) compared with before infection. Infectious keratitis is a common complication of LSCD associated with SJS or severe chemical burn to the cornea. Despite medical and surgical treatments, the visual outcome is poor.

  17. 1Restoration of ATM expression in DNA-PKcs deficient cells inhibits signal end joining

    Science.gov (United States)

    Neal, Jessica A.; Xu, Yao; Abe, Masumi; Hendrickson, Eric; Meek, Katheryn

    2016-01-01

    Unlike most DNA-PKcs deficient mouse cell strains, we show here that targeted deletion of DNA-PKcs in two different human cell lines abrogates VDJ signal end joining in episomal assays. Although the mechanism is not well defined, DNA-PKcs deficiency results in spontaneous reduction of ATM expression in many cultured cell lines (including those studied here) and in DNA-PKcs deficient mice. We considered that varying loss of ATM expression might explain differences in signal end joining in different cell strains and animal models, and we investigated the impact of ATM and/or DNA-PKcs loss on VDJ recombination in cultured human and rodent cell strains. To our surprise, in DNA-PKcs deficient mouse cell strains that are proficient in signal end joining, restoration of ATM expression markedly inhibits signal end joining. In contrast, in DNA-PKcs deficient cells that are deficient in signal end joining, complete loss of ATM enhances signal (but not coding) joint formation. We propose that ATM facilitates restriction of signal ends to the “classical” non-homologous end-joining pathway. PMID:26921311

  18. Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2018-01-01

    Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism.

  19. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Rashda [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Efferth, Thomas [Institute of Pharmacy und Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Kuhmann, Christine [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Opatz, Till [Institute of Organic Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz (Germany); Hao, Xiaojiang [Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204 (China); Popanda, Odilia, E-mail: o.popanda@dkfz.de [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2012-03-15

    Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC{sub 50} values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC{sub 50} values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy

  20. Implications of vitamin D deficiency in lithiasic patient and in general population.

    Science.gov (United States)

    Millán-Rodríguez, F; Gavrilov, P; Gracia-García, S; Angerri-Feu, O; Sánchez-Martín, F M; Villavicencio-Mavrich, H

    2015-05-01

    Vitamin D deficiency causes problems in mineral metabolism but also overall health. In first place a review of the topic was carried out. Then, in order to contextualize it in lithiasic patient, a study on Vitamin D deficiency and its possible relationship with impaired PTH levels is performed. A review of topics such as metabolism, epidemiology and the relationship of vitamin D deficiency with several pathologies was performed. Besides a multivariate analysis and a correlation study between vitamin D and PTH levels was conducted in 100 lithiasic patients. We present a review of Vitamin D metabolism, receptors and functions, as well as about its valuation methodology and the treatment of its deficiency. Lithiasic patients show a higher vitamin D deficiency than general population. Vitamin D deficiency has been significantly associated with increased PTH levels. In addition, there is enough literature showing a relationship between vitamin D deficiency not only with bone disease, but also with multiple diseases. vitamin D levels should be measured in all lithiasic patients, and those with vitamin D deficiency should be treated. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Common mutations in G6PD of Vietnamese-Kinh deficient patients ...

    African Journals Online (AJOL)

    This study was conducted to identify the common mutations occurring within the G6PD gene in the G6PD - Vietnamese deficient patients, which may be the main causative mutations of the G6PD deficiency in Vietnamese-kinh. Sequencing was performed to detect mutations in the coding region of G6PD gene for 30 ...

  2. Non-infectious lung disease in patients with adenosine deaminase deficient severe combined immunodeficiency.

    Science.gov (United States)

    Booth, C; Algar, V E; Xu-Bayford, J; Fairbanks, L; Owens, C; Gaspar, H B

    2012-06-01

    Adenosine deaminase deficiency is a disorder of purine metabolism manifesting severe combined immunodeficiency (ADA-SCID) and systemic abnormalities. Increased levels of the substrate deoxyadenosine triphosphate (dATP) lead to immunodeficiency and are associated in a murine model with pulmonary insufficiency. We compared a cohort of patients with ADA-SCID and X-linked SCID and found that despite similar radiological and respiratory findings, positive microbiology is significantly less frequent in ADA-SCID patients (p < 0.0005), suggesting a metabolic pathogenesis for the lung disease. Clinicians should be aware of this possibility and correct metabolic abnormalities either through enzyme replacement or haematopoietic stem cell transplant, in addition to treating infectious complications.

  3. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    Science.gov (United States)

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production.

  4. Regulatory T cells in the humoral response of protein deficient mice.

    Science.gov (United States)

    Price, P; Turner, K J

    1979-01-01

    Cell suspensions from the spleen or thymus of mice fed normally or mice that were protein deficient were injected into mice from each dietary group and also syngeneic nudes. Antigen, polyvinyl pyrrolidone (PVP), was injected at the stage of cell transfer and the antibody titres of the recipient animals were compared with those of control animals given only antigen. The regime was repeated using cell suspensions from donor animals which had been primed with antigen. These experiments showed that spleen cells were suppressive only when transferred from deficient to normal mice. Thymocytes generally lacked suppressive effects, except when given to irradiated mice also injected with "normal" spleen cells. However, thymocytes from deficient mice were marginally enhancing in nude mice, deficient mice and older "normals". To explain these results, it is suggested that responses to PVP are determined by distinct "suppressor-inducing" and "suppressor" T cells which act via helper T cells. The latter probably affect B cells directly and largely influence IgG production. It also appears likely that the ratio of helper to suppressor (inducer and effector) T cells is increased by protein deficiency.

  5. Cobalamin Deficiency in Elderly Patients: A Personal View

    Directory of Open Access Journals (Sweden)

    Emmanuel Andrès

    2008-01-01

    Full Text Available Cobalamin (vitamin B12 deficiency is particularly common in the elderly (>65 years of age but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and long-term ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption.

  6. TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed

    2006-01-01

    in cancer. In this regard, several studies have demonstrated an antiapoptotic effect of TIMP-1 in a number of different cell types. Since chemotherapy works by inducing apoptosis in cancer cells, we raised the hypothesis that TIMP-1 promotes resistance against chemotherapeutic drugs. In order to investigate...... this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...... deficiency increases the response to chemotherapy considerably, confirming that TIMP-1 protects the cells from apoptosis. This is to our knowledge the first study investigating TIMP-1 and chemotherapy-induced apoptosis employing a powerful model system comprising TIMP-1 gene-deficient cells...

  7. D-ribose therapy in four Polish patients with adenylosuccinate lyase deficiency: absence of positive effect.

    Science.gov (United States)

    Jurecka, A; Tylki-Szymanska, A; Zikanova, M; Krijt, J; Kmoch, S

    2008-12-01

    Deficiency of adenylosuccinate lyase (ADSL) (OMIM 103050) is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycle, diagnosed so far in approximately 50 patients. The clinical presentation is characterized by severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life. At present there is no treatment of proven clinical efficacy. Despite of the increasing number of ADSL-deficient patients reported, there are only a few communications of therapeutic considerations or efforts. Among them only two showed some beneficial effects in ADSL-deficient patients. D-ribose, a simple and relatively cheap therapy, has been associated with improvement of behaviour and progressive reduction of the seizure frequency in one 13-year-old patient with ADSL deficiency. In this study we have re-examined D-ribose treatment in four ADSL-deficient patients. Assessments consisted of biochemical markers and neurological outcome. The 12-month trial of D-ribose failed to show any clinical benefit in ADSL patients with both milder and severe phenotype. D-ribose administration was accompanied by neither reduction in seizure frequency nor growth enhancement. Additionally, patients with milder type II presented the first seizure after 4 and 8 months of the D-ribose treatment. Therefore, we could not confirm a positive effect of D-ribose as previously reported.

  8. Deficient Surrounding Rims in Patients Undergoing Transcatheter Atrial Septal Defect Closure.

    Science.gov (United States)

    Kijima, Yasufumi; Akagi, Teiji; Takaya, Yoichi; Taniguchi, Manabu; Nakagawa, Koji; Kusano, Kengo; Sano, Shunji; Ito, Hiroshi

    2016-08-01

    The influence of deficient rims surrounding atrial septal defects (ASDs) in patients undergoing transcatheter closure has yet to be clarified. The aim of this study was to assess the influence of a deficient surrounding rim on the procedural success and clinical outcome of transcatheter ASD closure using an Amplatzer septal occluder. A total of 474 patients (mean age, 46 ± 22 years) with ostium secundum ASDs measuring ≤40 mm in diameter who had undergone attempted transcatheter closure using Amplatzer septal occluders from September 2007 to August 2013 were assessed. A comprehensive transesophageal echocardiographic examination was done to assess the morphologic characteristics of the defects in all patients. Subjects were classified into three groups by the extent and location of rim deficiency (rims (sufficient group, n = 101), patients with single deficient rims, (single group, n = 338), and patients with multiple rim deficiencies (multiple group, n = 35). There was a significant difference in the maximal defect diameter among the sufficient, single, and multiple groups (15 ± 6, 18 ± 6, and 29 ± 7 mm, respectively, P rim deficiencies as determined by transesophageal echocardiography, successful transcatheter ASD closure using Amplatzer septal occluders is more difficult to accomplish. However, if closure is successful, rim deficiencies rarely affect intermediate-term outcomes. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  9. Turnover of beta-galactosidase in fibroblasts from patients with genetically different types of beta-galactosidase deficiency.

    OpenAIRE

    Van Diggelen, O P; Schram, A W; Sinnott, M L; Smith, P J; Robinson, D; Galjaard, H

    1981-01-01

    The turnover of lysosomal beta-galactosidase was studied in fibroblast cultures from patients with Gm1-gangliosidosis and combined beta-galactosidase and neuraminidase deficiency, which had 5-10% residual beta-galactosidase activity. beta-Galactosidase was specifically inactivated with the suicide substrate beta-D-galactopyranosylmethyl-p-nitro-phenyltriazene (beta-Gal-MNT) and from the subsequent restoration of enzyme activity in cell cultures turnover times were calculated. By using [3H]bet...

  10. Impression cytology implicates cell autophagy in aqueous deficiency dry eye

    Directory of Open Access Journals (Sweden)

    Lin T

    2017-04-01

    Full Text Available Tony Lin,1,2,* Richard Filek,3,* Joy M Wang,4 Chong H Wu,4 Hong Liu,2 Cindy ML Hutnik1–3 1Department of Ophthalmology, Western University, 2Ivey Eye Institute, St Joseph’s Health Care, St Joseph’s Hospital, 3Department of Pathology and Laboratory Medicine, 4Department of Biology, Western University, London, ON, Canada *These authors contributed equally to this work Purpose: Impression cytology in combination with a cell autophagy marker was used to demonstrate the utility of a novel frozen section technique, to assess the health of the ocular surface, as well as to correlate autophagic cell death with the commonly used clinical tests for dry eye. Methods: Female patients over the age of 18 years who attended an outpatient ophthalmology clinic were invited to participate. Schirmer’s test, tear film break-up time and the ocular surface disease index questionnaire were used as objective and subjective clinical tests for dry eye. The cellular biomarker microtubule-associated protein light chain 3 (LC3 was used as a marker of autophagic cell death. Results: Low LC3 nuclear staining was positively correlated with Schirmer’s test <10 mm. No correlation was found between other clinical tests for dry eye. Conclusion: This study demonstrates a positive linear relationship between Schirmer’s testing and LC3. There is a lack of correlation between the commonly used diagnostics tests for dry eye, highlighting our incomplete understanding and assessment of dry eye. Keywords: impression cytology, cell autophagy, dry eye, technique, Schirmer’s test, LC3

  11. Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells

    Directory of Open Access Journals (Sweden)

    Min Joo Kim

    2015-03-01

    Full Text Available BackgroundDamaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7-deficient β-cells.MethodsTo evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7F/F:RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction.ResultsBaseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05. Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05. By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05. Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1.ConclusionImpairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

  12. G6PD Deficiency Does Not Enhance Susceptibility for Acquiring Helicobacter pylori Infection in Sardinian Patients.

    Science.gov (United States)

    Dore, Maria Pina; Marras, Giuseppina; Rocchi, Chiara; Soro, Sara; Pes, Giovanni Mario

    2016-01-01

    Subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be more susceptible to infections due to impaired leukocyte bactericidal activity. The disorder is common in the Mediterranean area. The aim of this study was to investigate whether G6PD deficiency may be a risk factor for acquiring H. pylori infection. We performed a retrospective study. Data from clinical records of 6565 patients (2278 men and 4287 women, median age 51, range 7‒94) who underwent upper endoscopy between 2002 and 2014 were collected. H. pylori status, assessed by histology plus rapid urease test or 13C-urea breath test, and G6PD status were also reported. A multiple logistic regression model was used to investigate the association between G6PD deficiency and H. pylori infection. Enzyme deficiency was detected in 12% (789/6565) of the entire cohort, and more specifically in 8.3% of men and in 14.0% of women. Overall, the proportion of patients positive for H. pylori was 50.6% and 51.5% among G6PD deficient and non-deficient patients (χ² = 0.271; p = 0.315). Moreover, among G6PD-deficient and normal patients the frequency of previous H. pylori infection was similar. After adjustment for age and gender the risk for acquiring H. pylori infection was similar in G6PD-deficient and normal patients. Only age was a strong statistically significant risk predictor. These results demonstrate for the first time that G6PD deficiency does not enhance patients' susceptibility to acquire H. pylori infection in Sardinia.

  13. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Petersen, Eva Rosa; Kempfner, Jacob; Gammeltoft, Steen; Sorensen, Helge Bjarup Dissing; Jennum, Poul

    2013-01-01

    Several studies have suggested that hypocretin-1 may influence the cerebral control of the cardiovascular system. We analyzed whether hypocretin-1 deficiency in narcolepsy patients may result in a reduced heart rate response. We analyzed the heart rate response during various sleep stages from a 1-night polysomnography in patients with narcolepsy and healthy controls. The narcolepsy group was subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 67 narcolepsy patients and 22 control subjects were included in the study. Cataplexy was present in 46 patients and hypocretin-1 deficiency in 38 patients. None. All patients with narcolepsy had a significantly reduced heart rate response associated with arousals and leg movements (P hypocretin-1 deficiency and cataplexy groups compared with patients with normal hypocretin-1 levels (P hypocretin-1 deficiency significantly predicted the heart rate response associated with arousals in both REM and non-REM in a multivariate linear regression. Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest.

  14. A patient with bulimia nervosa and profound folate deficiency.

    Science.gov (United States)

    Eedy, D. J.; Curran, J. G.; Andrews, W. J.

    1986-01-01

    A case is reported of a young woman with bulimia nervosa who presented with profound folate deficiency. This association has not been reported before despite the increased theoretical possibility. Initially she has responded well to folic acid therapy and social support. PMID:3809077

  15. B-cell memory and primary immune deficiencies: interleukin-21 related defects.

    Science.gov (United States)

    Desjardins, Marylin; Mazer, Bruce D

    2013-12-01

    The purpose of this study is to describe recent advances in our understanding of the role of interleukin-21 (IL-21) in B-cell maturation, and how defects in IL-21 receptor (IL-21R) signalling pathways (IL-21R/γc/JAK3/STAT3) are related to primary immune deficiencies. Abnormal signalling through IL-21R/γc/JAK3/STAT3 pathway has been related to decreased specific antibody responses following vaccination, and to increased susceptibility to encapsulated bacterial infections. This is manifested in the hyper-IgE syndrome, X-linked and JAK3-related severe combined immunodeficiency (SCID) and loss-of-function mutations in the IL-21R gene. Common variable immunodeficiency is associated with impaired in-vitro development of peripheral blood mononuclear cells or purified B-cells into memory or CD38 B-cells following addition of IL-21. IL-21 is a key cytokine in development of B-cells into immunoglobulin-secreting cells. Abnormal signalling through the IL-21R/γc/JAK3/STAT3 pathway leads to defective humoral immune responses to both T-dependent and T-independent antigens and impairs the establishment of long-lasting B-cell memory. Studies involving patients with hyper-IgE syndrome demonstrated the nonredundant role of STAT3 in B-cell production of high-affinity specific antibodies, while total serum immunoglobulins could be maintained through STAT3-independent activation of AID (activation-induced cytidine-deaminase). IL-21 related defects may also be associated with reduced natural killer (NK)-cell cytotoxicity and TH17 cytokine production, indicating that abnormalities in the IL-21-IL-21R pathway have profound effects on crucial immune responses.

  16. HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jana Kudová

    Full Text Available Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1α-dependent mechanisms. However, the direct impact of HIF-1α deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1α deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes. It was accompanied with lower mRNA and protein levels of cardiac cell specific markers (myosin heavy chains 6 and 7 and with a decreasing percentage of myosin heavy chain α and β, and cardiac troponin T-positive cells. As to structural aspects of the differentiated cardiomyocytes, the localization of contractile proteins (cardiac troponin T, myosin heavy chain α and β and the organization of myofibrils were also different. Simultaneously, HIF-1α deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1α deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha. These findings thus suggest that HIF-1α deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro.

  17. HIF-1alpha Deficiency Attenuates the Cardiomyogenesis of Mouse Embryonic Stem Cells.

    Science.gov (United States)

    Kudová, Jana; Procházková, Jiřina; Vašiček, Ondřej; Perečko, Tomáš; Sedláčková, Miroslava; Pešl, Martin; Pacherník, Jiří; Kubala, Lukáš

    2016-01-01

    Cardiac cell formation, cardiomyogenesis, is critically dependent on oxygen availability. It is known that hypoxia, a reduced oxygen level, modulates the in vitro differentiation of pluripotent cells into cardiomyocytes via hypoxia inducible factor-1alpha (HIF-1α)-dependent mechanisms. However, the direct impact of HIF-1α deficiency on the formation and maturation of cardiac-like cells derived from mouse embryonic stem cells (mESC) in vitro remains to be elucidated. In the present study, we demonstrated that HIF-1α deficiency significantly altered the quality and quantity of mESC-derived cardiomyocytes. It was accompanied with lower mRNA and protein levels of cardiac cell specific markers (myosin heavy chains 6 and 7) and with a decreasing percentage of myosin heavy chain α and β, and cardiac troponin T-positive cells. As to structural aspects of the differentiated cardiomyocytes, the localization of contractile proteins (cardiac troponin T, myosin heavy chain α and β) and the organization of myofibrils were also different. Simultaneously, HIF-1α deficiency was associated with a lower percentage of beating embryoid bodies. Interestingly, an observed alteration in the in vitro differentiation scheme of HIF-1α deficient cells was accompanied with significantly lower expression of the endodermal marker (hepatic nuclear factor 4 alpha). These findings thus suggest that HIF-1α deficiency attenuates spontaneous cardiomyogenesis through the negative regulation of endoderm development in mESC differentiating in vitro.

  18. Anemia attributed to vitamin B6 deficiency in post-pancreaticoduodenectomy patients.

    Science.gov (United States)

    Yasuda, Hajime; Fujiwara, Noriko; Ishizaki, Yoichi; Komatsu, Norio

    2015-01-01

    Micronutrient deficiencies such as vitamin A, iron, zinc, and selenium have been known to occur as a consequence of pancreaticoduodenectomy (PD), but vitamin B6 deficiency has not been previously reported. We report two post-PD patients who developed anemias attributed to vitamin B6 deficiency. Oral supplementations of vitamin B6 significantly improved anemias in both cases. Micronutrients including vitamin B6 should be monitored in post-PD patients, and supplementations should be carried out when necessary. Copyright © 2014 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  19. Vitamin D deficiency is common in psychogeriatric patients, independent of diagnosis

    OpenAIRE

    Grønli, Ole Kristian; Kvamme, Jan-Magnus; Jorde, Rolf; Wynn, Rolf

    2014-01-01

    This article is part of Ole Kristian Grønli's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/6930 Background:Previous studies have found an association between psychiatric disorders and vitamin D deficiency, but most studies have focused on depression. This study aimed to establish the prevalence of vitamin D deficiency in elderly patients with a wider range of psychiatric diagnoses. Method: The study included elderly patients (>64 years) referred to a ps...

  20. Zinc-deficiency acrodermatitis in a patient with chronic alcoholism and gastric bypass: a case report

    Directory of Open Access Journals (Sweden)

    Dariush Shahsavari

    2014-07-01

    Full Text Available Acquired adult-onset zinc deficiency is occasionally reported in patients with malnutrition states, such as alcoholism, or malabsorptive states, such as post-bariatric surgery. The defining symptoms of hypozincemia include a classic triad of necrolytic dermatitis, diffuse alopecia, and diarrhea. We report a case of zinc deficiency in a 39-year-old man with history of gastric bypass surgery and alcoholism. For this patient, severe hypozincemia confirmed acrodermatitis, and zinc supplementation was met with gradual improvement.

  1. Perforin-deficient CD8+ T cells mediate fatal lymphocytic choriomeningitis despite impaired cytokine production

    DEFF Research Database (Denmark)

    Storm, Pernille; Bartholdy, Christina; Sørensen, Maria Rathmann

    2006-01-01

    Intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) is one of the most studied models for virus-induced immunopathology, and based on results from perforin-deficient mice, it is currently assumed that fatal disease directly reflects perforin-mediated cell lysis. However...... the outcome of i.c. infection with LCMV. We confirmed that the expansion of virus-specific CD8(+) T cells is unimpaired in perforin-deficient mice. However, despite the fact that the virus-specific CD8(+) effector T cells in perforin-deficient mice are broadly impaired in their effector function, these mice...... invariably succumb to i.c. infection with LCMV strain Armstrong, although a few days later than matched wild-type mice. Upon further investigation, we found that this delay correlates with the delayed recruitment of inflammatory cells to the central nervous system (CNS). However, CD8(+) effector T cells were...

  2. Relationship between cobalamin deficiency and delirium in elderly patients undergoing cardiac surgery

    Directory of Open Access Journals (Sweden)

    Sevuk U

    2015-08-01

    Full Text Available Utkan Sevuk,1 Erkan Baysal,2 Nurettin Ay,3 Yakup Altas,2 Rojhat Altindag,2 Baris Yaylak,2 Vahhac Alp,3 Ertan Demirtas4 1Department of Cardiovascular Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 2Department of Cardiology, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 3Department of General Surgery, Diyarbakir Gazi Yasargil Education and Research Hospital, Diyarbakir, 4Department of Cardiovascular Surgery, Liv Hospital, Ankara, Turkey Background: Delirium is common after cardiac surgery and is independently associated with increased morbidity, mortality, prolonged hospital stays, and higher costs. Cobalamin (vitamin B12 deficiency is a common cause of neuropsychiatric symptoms and affects up to 40% of elderly people. The relationship between cobalamin deficiency and the occurrence of delirium after cardiac surgery has not been examined in previous studies. We examined the relationship between cobalamin deficiency and delirium in elderly patients undergoing coronary artery bypass grafting (CABG surgery.Material and methods: A total of 100 patients with cobalamin deficiency undergoing CABG were enrolled in this retrospective study. Control group comprised 100 patients without cobalamin deficiency undergoing CABG. Patients aged 65 years or over were included. Diagnosis of delirium was made using Intensive Care Delirium Screening Checklist. Delirium severity was measured using the Delirium Rating Scale-revised-98.Results: Patients with cobalamin deficiency had a significantly higher incidence of delirium (42% vs 26%; P=0.017 and higher delirium severity scores (16.5±2.9 vs 15.03±2.48; P=0.034 than patients without cobalamin deficiency. Cobalamin levels were significantly lower in patients with delirium than patients without delirium (P=0.004. Delirium severity score showed a moderate correlation with cobalamin levels (Ρ=-0.27; P=0.024. Logistic regression analysis demonstrated that

  3. Oral supplementation of vitamin E reduces osmotic fragility of RBC in hemolytic anemic patients with G6PD deficiency

    International Nuclear Information System (INIS)

    Sultana, N.; Begum, S.; Begum, N.; Ali, T.

    2009-01-01

    Vitamin E has role in maintaining the integrity of red cell member by preventing oxidation of polyunsaturated fatty acids, thus protects cells from oxidative stress-induced lysis in G6PD deficiency. Changes in osmotic fragility of RBC and some absolute values like MCV, MCH and MCHC may occur in haemolytic anaemic patients with G6PD deficiency. To observe the effects of vitamin E supplementation on these changes in order to evaluate the role of this anti-oxidant vitamin in reducing chronic haemolysis in G6PD deficient patients. A total number of 102 subjects with age ranged of 5 to 40 years of both sexes were included in the study. Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (experimental group) and 34 were in non-supplemented group (control group). The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children ?12 years (in a divided dose, i.e., 4 times daily). Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the base line data (healthy control) and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD) of Haematology, Banglabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2005 to June 2006 and all healthy subjects were selected from personal contact. Blood G6PD level, osmotic fragility of RBC were measured by standard techniques and MCV, MCH, and MCHC were obtained by calculation. All the parameters were measured on day 1 of their first visit and also were on day 60 in deficient group. Data were compared among the deficient groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Mean starting and completing points of osmotic fragility of RBC were significantly higher but MCV. MCH, MCHC were significantly lower in patients suffering from

  4. Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.

    Science.gov (United States)

    Audemard-Verger, A; Descloux, E; Ponard, D; Deroux, A; Fantin, B; Fieschi, C; John, M; Bouldouyre, A; Karkowsi, L; Moulis, G; Auvinet, H; Valla, F; Lechiche, C; Davido, B; Martinot, M; Biron, C; Lucht, F; Asseray, N; Froissart, A; Buzelé, R; Perlat, A; Boutboul, D; Fremeaux-Bacchi, V; Isnard, S; Bienvenu, B

    2016-05-01

    Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14

  5. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations.

    Science.gov (United States)

    Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua; Jing, Pu

    2017-01-01

    The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF- γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN- γ . Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

  6. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

    Directory of Open Access Journals (Sweden)

    Bingjun Qian

    2017-01-01

    Full Text Available The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

  7. A Patient with Complex I Deficiency Caused by a Novel ACAD9 Mutation Not Responding to Riboflavin Treatment

    DEFF Research Database (Denmark)

    Nouws, Jessica; Wibrand, Flemming; van den Brand, Mariël

    2014-01-01

    fibroblasts partially rescued the complex I deficiency. Riboflavin supplementation did not ameliorate the complex I deficiency in patient fibroblasts. More than a dozen ACAD9 patients with complex I deficiency have been identified in the last 3 years, indicating that ACAD9 is important for complex I assembly...

  8. Bilateral leukocoria in a patient with homozygous protein C deficiency

    International Nuclear Information System (INIS)

    Khan, Nasrat M.; Al-Dohayan, Noura D.; Al-Batiniji, Fatima S.

    2007-01-01

    We describe a bilateral leukocoria and neonatal purpura fulminans in a male infant, born at full term after an unremarkable pregnancy to a healthy consanguineous married couple. Multiple hemorrhagic skin bullae were found at birth on various parts of the body with bilateral leukocoria, organized vitreous hemorrhage, retinal detachment, and intracranial hemorrhage with undetectable levels of protein C activity. We report a clinical case of homozygous protein-C deficiency with severe purpura fulminans and bilateral leukocoria. (author)

  9. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

    OpenAIRE

    Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua; Jing, Pu

    2017-01-01

    The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immun...

  10. Diagnosis, treatment and follow-up of patients with tetrahydrobiopterin deficiency in Shandong province, China.

    Science.gov (United States)

    Han, Bingjuan; Zou, Hui; Han, Bingchao; Zhu, Weiwei; Cao, Zhiyang; Liu, Yingxia

    2015-06-01

    To summarize the clinical and biochemical data, mutation analysis, treatment, outcome and the follow-up data of patients with BH4 deficiency from 2004 to 2012 in Shandong province, China. We analyzed the clinical, biochemical and treatment data of 40 patients with BH4 deficiency. Urinary neopterin and biopterin were analyzed. Further BH4 loading tests were performed in suspected patients with abnormal urinary pterin profiles. The patients with BH4 deficiency were treated with BH4 and neurotransmitter after diagnosis. Blood phenylalanine level, clinical symptoms and mental development were followed up. 40 cases with BH4 deficiency were identified and all classified as PTPS deficiency between 2004 and 2012 in Shandong province, China. They were diagnosed at the age of 20d - 41m and most patients received treatment with BH4, l-dopa and 5-HTP after diagnosis. Seven different mutations (P87S, K91R, T106M, D96N, N52S, S21R, and L127F) were detected in 11 patients. But outcome assessments were not always available. We obtained 19 records of DQ/IQ assessment. In 9 patients (7 early and 2 late diagnosed) no development delay is observed, while in 10 patients (8 early and 2 late diagnosed) development was delayed. Our study emphasized that screening for BH4 deficiency should be carried out in all patients with HPA in order to minimize misdiagnosis. Although the outcomes of BH4 deficiency are highly variable, early diagnosis and treatment is essential for good outcomes. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells.

    Science.gov (United States)

    Astuti, Puji; D Utami, Esti; Nugrahani, Arsa W; Sudjadi, Sismindari

    2012-11-30

    The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be "back to nature" and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane), a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM) induced cell proliferation, addition of genistein (20 μM) 16 h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM) induced necrotic cells. Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method could potentially be developed as an

  12. Genistein abrogates G2 arrest induced by curcumin in p53 deficient T47D cells

    Science.gov (United States)

    2012-01-01

    Background The high cost and low level of cancer survival urge the finding of new drugs having better mechanisms. There is a high trend of patients to be “back to nature” and use natural products as an alternative way to cure cancer. The fact is that some of available anticancer drugs are originated from plants, such as taxane, vincristine, vinblastine, pacitaxel. Curcumin (diferuloylmethane), a dietary pigment present in Curcuma longa rizhome is reported to induce cell cycle arrest in some cell lines. Other study reported that genistein isolated from Glycine max seed inhibited phosphorylation of cdk1, gene involved during G2/M transition and thus could function as G2 checkpoint abrogator. The inhibition of cdk1 phosphorylation is one of alternative strategy which could selectively kill cancer cells and potentially be combined with DNA damaging agent such as curcumin. Methods T47D cell line was treated with different concentrations of curcumin and genistein, alone or in combination; added together or with interval time. Flow Cytometry and MTT assay were used to evaluate cell cycle distribution and viability, respectively. The presence of apoptotic cells was determined using acridine orange-ethidium bromide staining. Results In this study curcumin induced G2 arrest on p53 deficient T47D cells at the concentration of 10 μM. Increasing concentration up to 30 μM increased the number of cell death. Whilst genistein alone at low concentration (≤10 μM) induced cell proliferation, addition of genistein (20 μM) 16 h after curcumin resulted in more cell death (89%), 34% higher than that administered at the same time (56%). The combination treatment resulted in apoptotic cell death. Combining curcumin with high dose of genistein (50 μM) induced necrotic cells. Conclusions Genistein increased the death of curcumin treated T47D cells. Appropriate timing of administration and concentration of genistein determine the outcome of treatment and this method

  13. Growth retardation due to idiopathic growth hormone deficiencies: MR findings in 24 patients

    International Nuclear Information System (INIS)

    Ochi, M.; Morikawa, M.; Yoshimoto, M.; Kinoshita, E.; Hayashi, K.

    1992-01-01

    In this study we evaluated the pituitary-hypothalamic abnormalities of ''idiopathic growth hormone (GH) deficiency'' as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with ''idiopathic GH deficiency'' had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life. (orig./GD)

  14. Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hansen, Christian S; Jensen, Jan S; Ridderstråle, Martin

    2017-01-01

    AIMS: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients. METHODS: 469 ambulatory type 2 diabetes patients (mean diabetes dura...

  15. Smac deficiency affects endoplasmic reticulum stress-induced apoptosis in human colon cancer cells

    Science.gov (United States)

    He, Qin; Shi, Jingxue; Jones, Samantha; An, Jie; Liu, Yuxin; Huang, Ying; Sheikh, M. Saeed

    2009-01-01

    Thapsigargin (TG) is a sesquiterpen lactone that inhibits the endoplasmic reticulum (ER) calcium ATPases to disrupt calcium homeostasis and consequently induces ER stress. We have previously reported that TG induces apoptosis by engaging the death receptor 5 (DR5) and the intrinsic pathways. Second mitochondrial-derived activator (Smac) is an important modulator of apoptosis that induces activation of caspases by antagonizing inhibitors of apoptosis (IAPs). In this study, we have utilized Smac-proficient and -deficient human colon cancer cells to investigate the effects of Smac deficiency during ER-stress-induced apoptosis. Our results indicate that Smac deficiency considerably affects ER stress-induced apoptosis in human colon cancer cells. For example, ER stress inducing agent TG upregulates DR5, and activates caspases 3, 9 and 8 in Smac-proficient cells. In Smac-deficient cells, although TG-induced DR5 upregulation is not affected, activation of caspases 3, 9 and 8 is affected. Smac deficiency also affects TG-induced cytochrome c release from mitochondria into cytosol suggesting the existence of a potential cross-talk between Smac and cytochrome c. Thus, our results indicate that ER stress-induced apoptosis also engages Smac for transduction of apoptotic signals in human colon cancer cells and that a potential feedback signaling between Smac and cytochrome c appears to modulate the intrinsic pathway of apoptosis. PMID:20209078

  16. Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD.

    Directory of Open Access Journals (Sweden)

    Brian N McCullagh

    Full Text Available Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8, specific antibody deficiency (20, and selective IgA deficiency (1. Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies

  17. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Directory of Open Access Journals (Sweden)

    Tongfang Tang

    Full Text Available BACKGROUND: Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD through alternation of liver innate immune response. AIMS: The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. METHODS: Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. RESULTS: High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4 expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. CONCLUSION: High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  18. Pro-inflammatory activated Kupffer cells by lipids induce hepatic NKT cells deficiency through activation-induced cell death.

    Science.gov (United States)

    Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

    2013-01-01

    Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD.

  19. [Prevalence and characteristics of anemia and iron deficiency in patients hospitalized for gastrointestinal diseases in Spain].

    Science.gov (United States)

    Mearin, Fermín; Barreiro-de Acosta, Manuel; González-Galilea, Ángel; Gisbert, Javier P; Cucala, Mercedes; Ponce, Julio

    2013-10-01

    To determine the prevalence and characteristics of anemia and iron deficiency in patients hospitalized for gastrointestinal diseases. An epidemiological, multicenter, mixed design study (retrospective review of randomized clinical records and prospective visits) conducted between February 2010 and March 2011 in 22 Spanish gastroenterology departments. Severe anemia was defined as Hb < 10g/dL, mild/moderate as Hb ≥ 10g/dL, and iron deficiency as ferritin < 30ng/ml or transferrin saturation < 16%. We included 379 patients. The mean±SD age was 57±19 years and 47% were men. The prevalence of anemia at admission was 60% (95% CI 55 to 65), and anemia was severe (Hb <10g/dl) in half the patients. The prevalence of iron deficiency was 54% of evaluable patients (95% CI 47 to 61). Gastrointestinal bleeding at admission was found in 39% of the patients, of whom 83% (121/146) were anemic. At discharge, the proportion of anemic patients was unchanged (from 60% at admission to 58% at discharge) (95% CI 53 to 63) and iron deficiency was found in 41% (95% CI 32 to 50): anemia was severe in 17% and mild/moderate in 41%. During follow-up, at 3-6 months after admission, 44% (95% CI 39 to 50) of evaluable patients continued to have iron deficiency and 28% (95% CI 23 to 32) were still anemic: 5% severe and 23% mild/moderate. The prevalence of iron deficiency was 44% (95% CI: 39-50). During admission, 50% of patients with anemia did not receive treatment. At discharge, 55% were untreated. The prevalence of anemia in patients hospitalized for gastroenterological diseases was very high. Anemia persisted in over a quarter of patients at the follow-up visit. Only half of hospitalized patients received treatment for anemia, even when the anemia was severe. Copyright © 2013 Elsevier España, S.L. y AEEH y AEG. All rights reserved.

  20. Development and implementation of a novel assay for L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) in cell lysates: L-2-HGDH deficiency in 15 patients with L-2-hydroxyglutaric aciduria

    DEFF Research Database (Denmark)

    Kranendijk, M; Salomons, G S; Gibson, K M

    2009-01-01

    L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by mutations in the gene encoding L-2-hydroxyglutarate dehydrogenase. An assay to evaluate L-2-hydroxyglutarate dehydrogenase (L-2-HGDH) activity in fibroblast, lymphoblast and/or lymphoc...... the relationship between molecular and biochemical observations. Residual activity was detected in cells derived from one L-2-HGA patient. The L-2-HGDH assay will be valuable for examining in vitro riboflavin/FAD therapy to rescue L-2-HGDH activity....

  1. Dedicator of cytokinesis 8-deficient CD4+T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells.

    Science.gov (United States)

    Tangye, Stuart G; Pillay, Bethany; Randall, Katrina L; Avery, Danielle T; Phan, Tri Giang; Gray, Paul; Ziegler, John B; Smart, Joanne M; Peake, Jane; Arkwright, Peter D; Hambleton, Sophie; Orange, Jordan; Goodnow, Christopher C; Uzel, Gulbu; Casanova, Jean-Laurent; Lugo Reyes, Saul Oswaldo; Freeman, Alexandra F; Su, Helen C; Ma, Cindy S

    2017-03-01

    Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4 + T cells to disease pathogenesis in these patients has not been thoroughly investigated. We sought to investigate the phenotype and function of DOCK8-deficient CD4 + T cells to determine (1) intrinsic and extrinsic CD4 + T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency. We performed in-depth analysis of the CD4 + T-cell compartment of DOCK8-deficient patients. We enumerated subsets of CD4 + T helper cells and assessed cytokine production and transcription factor expression. Finally, we determined the levels of IgE specific for staple foods and house dust mite allergens in DOCK8-deficient patients and healthy control subjects. DOCK8-deficient memory CD4 + T cells were biased toward a T H 2 type, and this was at the expense of T H 1 and T H 17 cells. In vitro polarization of DOCK8-deficient naive CD4 + T cells revealed the T H 2 bias and T H 17 defect to be T-cell intrinsic. Examination of allergen-specific IgE revealed plasma IgE from DOCK8-deficient patients is directed against staple food antigens but not house dust mites. Investigations into the DOCK8-deficient CD4 + T cells provided an explanation for some of the clinical features of this disorder: the T H 2 bias is likely to contribute to atopic disease, whereas defects in T H 1 and T H 17 cells compromise antiviral and antifungal immunity, respectively, explaining the infectious susceptibility of DOCK8-deficient patients. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

  2. Prevalence of G6PD deficiency in a large cohort of HIV-infected patients.

    Science.gov (United States)

    Serpa, Jose A; Villarreal-Williams, Erick; Giordano, Thomas P

    2010-11-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. Screening for this condition in HIV-infected patients from susceptible ethnic groups is recommended based on expert opinion. Here we determined the prevalence of G6PD deficiency and the occurrence of G6PD-related hemolytic events in a large cohort of patients. We identified all HIV-infected adults who presented as new patients at a single urban HIV clinic between 02/01/2007 and 01/31/2009. Demographic and laboratory data including G6PD results were collected. In addition, outpatient and inpatient medical records of G6PD deficient patients were reviewed for episodes of hemolytic anemia. A total of 1172 patients were identified and G6PD testing was performed in 1110 (94.7%). Overall, 75 (6.8%) subjects had G6PD deficiency. Rates were higher among African Americans (68/699; 9.7%) and Hispanics (5/253; 2.0%). Only one non-Hispanic White subject had G6PD deficiency (1/153; 0.7%). At baseline, hemoglobin concentrations were similar among subjects with or without G6PD deficiency. Among patients with G6PD deficiency, 40 (53.3%) were prescribed trimethoprim-sulfamethoxazole or dapsone. During follow-up, five (6.7%) of these patients developed acute hemolytic anemia. These results provide strong clinical evidence for recommending G6PD testing in HIV-infected subjects from susceptible ethnic backgrounds. Copyright © 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

  3. Adenylosuccinate lyase deficiency: the first identified polish patient.

    Science.gov (United States)

    Jurkiewicz, Elzbieta; Mierzewska, Hanna; Kuśmierska, Katarzyna

    2007-10-01

    Adenylosuccinate lyase (ADSL) deficiency is a rare disease of de novo purine synthesis. The main symptoms are psychomotor retardation, epilepsy, autistic features, occasionally associated with muscular hypotonia. Diagnosis is made by detection of abnormal purine metabolites (succinyladenosine - S-Ado and succinylaminoimidazole carboxamide riboside - SAICAr) in body fluids. The severity of the clinical features correlates with low S-Ado/SAICAr ratio. We report clinical, biochemical and brain MRI findings of a female infant with severe early epilepsy and hypotonia, who died at the age of 10 weeks.

  4. The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.

    1983-08-01

    The capacity of spleen and peritoneal cells from iron deficient mice, ad libitum fed control mice, and pair-fed mice to kill allogenic tumor cells (mastocytoma tumor P815) has been investigated. In the first study, mice were sensitized in vivo with 10(7) viable tumor cells 51 and 56 days after weaning. The capacity of splenic cells and peritoneal cells from sensitized and nonsensitized mice to kill tumor cells was evaluated 5 days after the second dose of tumor cells. At ratios of 2.5:1 to 100:1 of attacker to target cells, the percentage /sup 51/Cr release after 4 h of incubation was significantly less in iron-deficient mice than control and/or pair-fed mice (p less than 0.05). Protein-energy undernutrition in pair-fed mice had no significant effect. In the second study, spleen cells and enriched T cell fractions were incubated in vitro for 5 days with uv irradiated Balb/C spleen cells in a 2:1 ratio. The cytotoxic capacity against the same allogenic tumor cells was again evaluated. The percentage chromium release at different attacker to target cells was less than 30% in the iron-deficient group compared to either control or pair-fed supporting the results of in vivo sensitized cells. The possible mode of impairment of the cytotoxic capacity is discussed.

  5. Effects of Oral Supplementation of Vitamin E on Fragility of RBC in Hemolytic Anemic Patients with G6PD Deficiency

    Directory of Open Access Journals (Sweden)

    Nayma Sultana

    2009-11-01

    Full Text Available Background: Vitamin E has role in maintaining the integrity of red cell membrane by preventing oxidation of polyunsaturated fatty acids and thereby protects cells from oxidative stress- induced lysis in G6PD deficiency, which can be reflected by changes in osmotic fragility of RBC and some absolute values like MCV, MCH & MCHC. Objective: To observe the effects of vitamin E supplementation on fragility of RBC in order to evaluate role of this antioxidant vitamin in reducing chronic hemolysis in G6PD deficient patients. Methods: For this, a total number of 102 subjects with age ranged from 5 to 40 years of both sexes were included in the study. Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (study group and 34 were in non-supplemented group (control group. The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children < 12 years (in a divided dose i,e. 4 times daily. Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the base line data (healthy control and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD of Hematology, Bangabandhu Sheikh Mujib Medical University (BSMMU, Dhaka, Bangladesh during the period of July 2005 to June 2006 and all the healthy subjects were selected from personal contact. Blood G6PD level, osmotic fragility of RBC were measured by standard techniques and MCV, MCH, and MCHC were obtained by calculation. All the parameters were measured on day 1 (one of their first visit and also were on day 60 in deficient group. Data were compared among the deficient groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Results: Mean starting and completing points of osmotic fragility of RBC were significantly higher but MCV, MCH, MCHC were

  6. Attenuated Heart Rate Response is Associated with Hypocretin Deficiency in Patients with Narcolepsy

    DEFF Research Database (Denmark)

    Sørensen, Gertrud Laura; Knudsen, Stine; Petersen, Eva Rosa

    2013-01-01

    Our results show that autonomic dysfunction is part of the narcoleptic phenotype, and that hypocretin-1 deficiency is the primary predictor of this dysfunction. This finding suggests that the hypocretin system participates in the modulation of cardiovascular function at rest. CITATION: Sorensen GL......; Knudsen S; Petersen ER; Kempfner J; Gammeltoft S; Sorensen HBD; Jennum P. Attenuated heart rate response is associated with hypocretin deficiency in patients with narcolepsy. SLEEP 2013;36(1):91-98....

  7. Prevalence of Micronutrient Deficiency in Patients with Morbid Obesity Before Bariatric Surgery.

    Science.gov (United States)

    Krzizek, Eva-Christina; Brix, Johanna Maria; Herz, Carsten Thilo; Kopp, Hans Peter; Schernthaner, Gerit-Holger; Schernthaner, Guntram; Ludvik, Bernhard

    2018-03-01

    Postoperative micronutrient deficiency is a known side effect of bariatric surgery. In this study, we examined the prevalence of micronutrient deficiency in patients with morbid obesity (MO) preoperatively. A total of 1732 patients with MO wishing to undergo bariatric surgery (age: 40 ± 12 years, mean BMI: 44 ± 9 kg/m 2 , means ± SD, 77.3% female) were analyzed in this cross-sectional examination. Iron state, vitamin B12, folic acid, 25hydroxy(OH)-vitamin D, PTH, vitamin A, and vitamin E levels were determined. Subsequently, patients underwent nutritional counseling and were substituted accordingly. A total of 63.2% (n = 1094) of the patients had a deficit in folic acid ( 56.9 pg/ml). A total of 5.1% (n = 88) of the patients presented with a deficit in vitamin B12 (deficiency (ferritin deficiency (women 11.8% vs. men 1.5%, p prevalence of micronutrient deficiency in patients with morbid obesity preoperatively and emphasize the importance of exact preoperative evaluation and adequate substitution as well as postoperative surveillance.

  8. Risk Factors for Vitamin D, Zinc, and Selenium Deficiencies in Korean Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Han, Yoo Min; Yoon, Hyuk; Lim, Soo; Sung, Mi-Kyung; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung; Lee, Dong Ho; Kim, Joo Sung

    2017-05-15

    Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; pzinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn's disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients.

  9. Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome.

    Science.gov (United States)

    Murakami, Yoshiko; Kanzawa, Noriyuki; Saito, Kazunobu; Krawitz, Peter M; Mundlos, Stefan; Robinson, Peter N; Karadimitris, Anastasios; Maeda, Yusuke; Kinoshita, Taroh

    2012-02-24

    Hyperphosphatasia mental retardation syndrome (HPMR), an autosomal recessive disease characterized by mental retardation and elevated serum alkaline phosphatase (ALP) levels, is caused by mutations in the coding region of the phosphatidylinositol glycan anchor biosynthesis, class V (PIGV) gene, the product of which is a mannosyltransferase essential for glycosylphosphatidylinositol (GPI) biosynthesis. Mutations found in four families caused amino acid substitutions A341E, A341V, Q256K, and H385P, which drastically decreased expression of the PIGV protein. Hyperphosphatasia resulted from secretion of ALP, a GPI-anchored protein normally expressed on the cell surface, into serum due to PIGV deficiency. In contrast, a previously reported PIGM deficiency, in which there is a defect in the transfer of the first mannose, does not result in hyperphosphatasia. To provide insights into the mechanism of ALP secretion in HPMR patients, we took advantage of CHO cell mutants that are defective in various steps of GPI biosynthesis. Secretion of ALP requires GPI transamidase, which in normal cells, cleaves the C-terminal GPI attachment signal peptide and replaces it with GPI. The GPI-anchored protein was secreted substantially into medium from PIGV-, PIGB-, and PIGF-deficient CHO cells, in which incomplete GPI bearing mannose was accumulated. In contrast, ALP was degraded in PIGL-, DPM2-, or PIGX-deficient CHO cells, in which incomplete shorter GPIs that lacked mannose were accumulated. Our results suggest that GPI transamidase recognizes incomplete GPI bearing mannose and cleaves a hydrophobic signal peptide, resulting in secretion of soluble ALP. These results explain the molecular mechanism of hyperphosphatasia in HPMR.

  10. Lymphopenia-induced proliferation in Aire-deficient mice helps to explain their autoimmunity and differences from human patients

    Directory of Open Access Journals (Sweden)

    Kai eKisand

    2014-02-01

    Full Text Available Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED and its mouse model – both caused by mutant AIRE – have greatly advanced the under-standing of thymic processes that generate a self-tolerant T-cell repertoire. Much is now known about the molecular mechanisms by which AIRE induces tissue-specific antigen expression in thymic epithelium, and how this leads to negative selection of autoreactive thymocytes. However, we still do not understand the processes that lead to the activation of any infrequent naïve auto-reactive T-cells exported by AIRE-deficient thymi. Also, the striking phenotypic differences between APECED and its mouse models have puzzled researchers for years. The aim of this review is to suggest explanations for some of these unanswered questions, based on a fresh view of published experiments. We bring evidence that autoreactive T-cells can be activated by prolonged neonatal lymphopenia that naturally develops in young Aire-deficient mice due to delayed export of mature thymocytes. Lymphopenia induced proliferation (LIP fills the empty space favoring autoreactive T cells. This leads to lymphocyte infiltration in similar tissues as seen in day 3 thymectomised animals. LIP turns uncontrolled in Aire–/– crosses with other model mice with defects in genes responsible for anergy induction and Treg responsiveness, or defects in TCR signaling in combination with impaired function of homeostatic cytokines. In APECED patients LIP is probably not among the factors that participate in naïve autoreactive T cell activation as humans are born with more mature immune system in comparison to mice. We suggest that human AIRE-deficiency presents with different phenotype due to additional precipitating factors on top of deficient negative selection of tissue-specific thymocytes.

  11. Vitamin B12 deficiency in patients undergoing bariatric surgery: preventive strategies and key recommendations.

    Science.gov (United States)

    Majumder, Shounak; Soriano, Jose; Louie Cruz, Allan; Dasanu, Constantin A

    2013-01-01

    Advances in bariatric surgery have brought about a paradigm shift in the management of obesity, with benefits extending beyond weight loss. However, nutritional deficiencies are an inherent problem in the postoperative period and often require lifelong supplementation. Vitamin B12, also referred to as cobalamin, is one of the most common micronutrient deficiencies affecting this population. This review explores the pathophysiology of cobalamin deficiency in patients undergoing bariatric surgery and provides an overview of the effectiveness of various available vitamin B12 formulations. To identify the relevant literature, a systematic review of MEDLINE was conducted from the earliest dates through September 2012 for English-language articles describing the prevention and management of vitamin B12 deficiency in patients undergoing bariatric surgery. Intramuscular vitamin B12 continues to be the gold standard of therapy for vitamin B12 deficiency, especially in symptomatic patients. In select patients with asymptomatic vitamin B12 deficiency after Roux-en-Y gastric bypass (RYGB), high-dose oral cyanocobalamin should be given a consideration, especially when there are concerns with the adherence to intramuscular therapy or if compliance comes into question. Unlike patients post-RYGB, those undergoing restrictive procedures such as gastric banding and sleeve gastrectomy may be maintained postoperatively on a lower-dose daily vitamin B12 supplementation. Efficacy data of nasal and sublingual routes for maintenance therapy is currently awaited. Patients undergoing bariatric surgery must be continuously educated on proper nutrition, the risk of developing significant vitamin B12 deficiency, and the role of supplements in avoiding catastrophic consequences. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  12. Isolation of human immune deficiency virus from African AIDS patients and from persons without AIDS or IgG antibody to human immune deficiency virus.

    Science.gov (United States)

    McCormick, J B; Krebs, J W; Mitchell, S W; Feorino, P M; Getchell, J P; Odio, W; Kapita, B; Quinn, T C; Piot, P

    1987-01-01

    We previously reported a high incidence of acquired immune deficiency syndrome (AIDS) in Kinshasa, Zaire, as well as a high frequency of antibody to human immunodeficiency virus (HIV), which includes HTLV-III and LAV viruses, in persons without AIDS. In this report we assessed the frequency of HIV virus infection in persons with and without clinical AIDS and the association of virus isolation to presence of antibody. We isolated HIV from 27 (77%) of 35 patients with AIDS, and 5 of 9 patients with AIDS-related complex (ARC). Virus was also isolated from plasma and cerebrospinal fluid of patients in the study. The presence of antibody was a reliable marker for virus infection in African patients with AIDS. HIV was isolated from 5 of 27 control patients without AIDS, 3 of whom had normal T helper to T suppressor ratios and normal numbers of T helper cells. Two of these patients had no detectable antibody to HIV by ELISA or Western blot methods. In a population, such as the general heterosexual population of Kinshasa, with frequent infection by HIV and with few clearly definable risk groups, screening for antibodies to HIV may not be sufficient to identify some virus infected persons.

  13. Red cell distribution width in the diagnosis of iron deficiency anemia and thalassemia trait

    International Nuclear Information System (INIS)

    Adil, M.M.; Junaid, A.; Zaman, I.; Ishtiaque, Z.B.

    2010-01-01

    To evaluate diagnostic importance of Red Cell Distribution Width (RDW) in differentiating iron deficiency anemia from Thalassemia trait. A total of 100 cases aged 5 months to 50 years of either sex with diagnosed iron deficiency anemia or thalassemia trait were compared with respect to their RDW value. RDW value in iron deficiency anemia was between 36.2% to 55.2% (Mean 44.1%). The range of RDW in Thalassemia trait was 14.7% to 24.9% (Mean 19.8%). Conclusions The very high range of RDW in iron deficiency anemia as compared to slight elevation of the value in thalassemia trait in our study suggests that RDW value obtained from simple Complete Blood Counts (CBC) can help in differentiating the two pathologies. (author)

  14. Medication adherence to oral iron therapy in patients with iron deficiency anemia.

    Science.gov (United States)

    Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

    2016-01-01

    This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment.

  15. Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency.

    Science.gov (United States)

    Borte, Stephan; Pan-Hammarström, Qiang; Liu, Chonghai; Sack, Ulrich; Borte, Michael; Wagner, Ulf; Graf, Dagmar; Hammarström, Lennart

    2009-11-05

    Interleukin-21 (IL-21) is an important promoter for differentiation of human B cells into immunoglobulin (Ig)-secreting cells. The objective of this study was to evaluate an IL-21-based approach to induce immunoglobulin production in B cells from patients with common variable immunodeficiency (CVID) or selective IgA deficiency (IgAD). We show that a combination of IL-21, IL-4, and anti-CD40 stimulation induces class-switch recombination to IgG and IgA and differentiation of Ig-secreting cells, consisting of both surface IgG(+) (sIgG(+)) and sIgA(+) B cells and CD138(+) plasma cells, in patients with CVID or IgAD. Stimulation with IL-21 was far more effective than stimulation with IL-4 or IL-10. Moreover, spontaneous apoptosis of CD19(+) B cells from patients with CVID or IgAD was prevented by a combination of IL-21, IL-4, and anti-CD40 stimulation. Analysis of IL-21 and IL-21 receptor (IL-21R) mRNA expression upon anti-CD3 stimulation of T cells, however, showed no evidence for defective IL-21 expression in CVID patients and sequencing of the coding regions of the IL21 gene did not reveal any mutations, suggesting a regulatory defect. Thus, our work provides an initial basis for a potential therapeutic role of IL-21 to reconstitute immunoglobulin production in CVID and IgAD.

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  17. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    International Nuclear Information System (INIS)

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-01-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted

  18. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ghorbanzadeh-Moghaddam, Amir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Gholamrezaei, Ali, E-mail: Gholamrezaei@med.mui.ac.ir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Poursina Hakim Research Institution, Isfahan (Iran, Islamic Republic of); Hemati, Simin [Department of Radiotherapy Oncology, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of)

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  19. Reduced MLH3 Expression in the Syndrome of Gan-Shen Yin Deficiency in Patients with Different Diseases.

    Science.gov (United States)

    Du, Juan; Zhong, Maofeng; Liu, Dong; Liang, Shufang; Liu, Xiaolin; Cheng, Binbin; Zhang, Yani; Yin, Zifei; Wang, Yuan; Ling, Changquan

    2017-01-01

    Traditional Chinese medicine formulates treatment according to body constitution (BC) differentiation. Different constitutions have specific metabolic characteristics and different susceptibility to certain diseases. This study aimed to assess the characteristic genes of gan-shen Yin deficiency constitution in different diseases. Fifty primary liver cancer (PLC) patients, 94 hypertension (HBP) patients, and 100 diabetes mellitus (DM) patients were enrolled and classified into gan-shen Yin deficiency group and non-gan-shen Yin deficiency group according to the body constitution questionnaire to assess the clinical manifestation of patients. The mRNA expressions of 17 genes in PLC patients with gan-shen Yin deficiency were different from those without gan-shen Yin deficiency. However, considering all patients with PLC, HBP, and DM, only MLH3 was significantly lower in gan-shen Yin deficiency group than that in non-gen-shen Yin deficiency. By ROC analysis, the relationship between MLH3 and gan-shen Yin deficiency constitution was confirmed. Treatment of MLH3 (-/- and -/+) mice with Liuweidihuang wan, classical prescriptions for Yin deficiency, partly ameliorates the body constitution of Yin deficiency in MLH3 (-/+) mice, but not in MLH3 (-/-) mice. MLH3 might be one of material bases of gan-shen Yin deficiency constitution.

  20. Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells.

    Science.gov (United States)

    Katz, Samuel G; Labelle, James L; Meng, Hailong; Valeriano, Regina P; Fisher, Jill K; Sun, Heather; Rodig, Scott J; Kleinstein, Steven H; Walensky, Loren D

    2014-02-06

    Mantle cell lymphoma (MCL) is a highly aggressive B-cell lymphoma resistant to conventional chemotherapy. Although defined by the characteristic t(11;14) translocation, MCL has not been recapitulated in transgenic mouse models of cyclin D1 overexpression alone. Indeed, several genetic aberrations have been identified in MCL that may contribute to its pathogenesis and chemoresistance. Of particular interest is the frequent biallelic deletion of the proapoptotic BCL-2 family protein BIM. BIM exerts its pro-death function via its α-helical BH3 death domain that has the dual capacity to inhibit antiapoptotic proteins such as BCL-2 and MCL-1 and directly trigger proapoptotic proteins such as the mitochondrial executioner protein BAX. To evaluate a functional role for Bim deletion in the pathogenesis of MCL, we generated cyclin D1-transgenic mice harboring Bim-deficient B cells. In response to immunization, Eμ(CycD1)CD19(CRE)Bim(fl/fl) mice manifested selective expansion of their splenic mantle zone compartment. Three distinct immune stimulation regimens induced lymphomas with histopathologic and molecular features of human MCL in a subset of mice. Thus, deletion of Bim in B cells, in the context of cyclin D1 overexpression, disrupts a critical control point in lymphoid maturation and predisposes to the development of MCL. This genetic proof of concept for MCL pathogenesis suggests an opportunity to reactivate the death pathway by pharmacologic mimicry of proapoptotic BIM.

  1. High incidence of Epstein-Barr virus (EBV)-positive Hodgkin lymphoma and Hodgkin lymphoma-like B-cell lymphoproliferations with EBV latency profile 2 in children with interleukin-2-inducible T-cell kinase deficiency.

    Science.gov (United States)

    Bienemann, Kirsten; Borkhardt, Arndt; Klapper, Wolfram; Oschlies, Ilske

    2015-11-01

    Interleukin-2-inducible T-cell kinase (ITK) deficiency is an inherited T-cell deficiency characterized by the development of Epstein-Barr virus (EBV)-associated lymphoproliferations. We aimed to describe the histopathological features of lymphoproliferative processes arising in ITK deficiency, and to compare them with lymphoproliferations in otherwise immunocompromised patients. We revised the histopathological diagnoses of 12 biopsies of lymphoproliferations from seven ITK-deficient children according to the World Health Organization criteria, and determined the EBV latency types and lytic activity by staining for EBV-encoded small RNA, latent membrane protein 1, EBV nuclear antigen 2, and ZEBRA. We found polymorphic and borderline polymorphic to monomorphic B-cell lymphoproliferations with variable contents in large cells (five cases), a Hodgkin-like B-cell proliferation (one case), and classic mixed-cellularity Hodgkin lymphoma (six cases). All cases (12/12) were EBV-positive. The Hodgkin lymphoma-like and Hodgkin lymphoma, and all but one polymorphic B-cell lymphoproliferation, showed EBV latency type 2, as observed in classic EBV-positive Hodgkin lymphoma. The 100% EBV association, the high percentage of EBV-positive classic Hodgkin lymphoma and Hodgkin-like B-cell proliferations and the predominance of EBV latency type 2 even in polymorphic lesions are the main features of lymphoproliferations in patients with ITK deficiency, and suggest a unique pathomechanism of lymphomagenesis in this T-cell immunodeficiency. © 2015 John Wiley & Sons Ltd.

  2. Radio-sensitization of WRN helicase deficient cancer cells by targeting homologous recombination pathway

    International Nuclear Information System (INIS)

    Gupta, Pooja; Saha, Bhaskar; Patro, Birija Sankar; Chattopadhyay, Subrata

    2016-01-01

    Ionizing radiation (IR) induced DNA double-strand breaks (DSBs) are primarily repaired by non-homologous end joining (NHEJ). However, it is well established that a subset DSBs which are accumulated in IR-induced G2 phase are dependent on homologous recombination (HR). DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyperdependent on DNA damage response pathways, including the CHK1-kinase-mediated HR-repair. These observations suggest that DNA repair deficient tumors should exhibit increased radio-sensitivity under HR inhibition. Genetic defects leading to functional loss of werner (WRN) protein is associated with genomic instability and increased cancer incidence. WRN function is known to be abrogated in several human cancer cells due to hypermethylation of CpGisland-promoter and transcriptional silencing of WRN gene. In the current investigation, using isogenic pairs of cell lines differing only in the WRN function, we showed that WRN-deficient cell lines were hyper-radiosensitive to CHK1 pharmacologic inhibition. Here, we found that unrepaired DSB was drastically increased in WRN-deficient cells vis-à-vis WRN-proficient cells in response to IR and CHK1 inhibitor (CHK1i). Our results revealed a marginal role of NHEJ pathway accountable for the radio-sensitivity of WRN-deficient cells. Interestingly, silencing CTIP, a HR protein required for RAD51 loading, significantly abrogated the CHK1i-mediated radiosensitivity in WRN-deficient cells. Silencing of WRN or CTIP individually led to no significant difference in the extent of DNA end resection, as required during HR pathway. Imperatively, our results revealed that WRN and CTIP together play a complementary role in executing DNA end resection during HR-mediated repair of IR induced DSBs. Altogether, our data indicated that inhibition of IR-induced HR pathway at RAD51 loading, but not at DSB end resection, make the WRN-deficient cancer cells

  3. Cerebellar Toxoplasmosis in an Immunocompetent Patient with G6PD Deficiency.

    Science.gov (United States)

    Harbada, Rishit K; Sorabjee, Jehangir S; Surya, Nirmal; Jadhav, Kishor A; Mirgh, Sumeet

    2016-08-01

    We report a case of an immunocompetent patient who presented with a short history of unilateral cerebellar lesion later proven as toxoplasmosis on histopathology. The case highlights that patients with G6PD deficiency are more prone to develop fatal toxoplasma infections than those individuals with normal G6PD activity. © Journal of the Association of Physicians of India 2011.

  4. Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients

    NARCIS (Netherlands)

    van der Kamp, H. J.; Otten, B. J.; Buitenweg, N.; de Muinck Keizer-Schrama, S. M. P. F.; Oostdijk, W.; Jansen, M.; Delemarre-de Waal, H. A.; Vulsma, T.; Wit, J. M.

    2002-01-01

    To evaluate growth from diagnosis until final height (FH) in 21-hydroxylase deficiency patients. A retrospective longitudinal study was performed. Only patients treated with hydrocortisone and fludrocortisone (in case of salt wasting) were evaluated. This resulted in a sample of 34 (21 male, 13

  5. Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

    DEFF Research Database (Denmark)

    Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

    2006-01-01

    identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH......OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium......-deficient and healthy males, indicating identical bone turnover. The GH-deficient females, however, had significantly lower levels of bone markers compared to healthy females, indicating a reduced bone turnover. Oestrogen substitution of the GH-deficient females could explain this difference. CONCLUSIONS: Compared...

  6. Vitamin D Deficiency in South Sharqiya in Oman and its Impact in ENT Patients- A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Hasan Abdul Cader Segana

    2016-12-01

    Full Text Available Introduction Vitamin D deficiency has multitude of causes and can present with varying clinical manifestations. Studies show that it can lead on to recurrent respiratory infections, ear infections and deafness. Vitamin D also has immunomodulant action. Here we discuss the varying features concerning an Otolaryngologist in general as far as Vitamin D metabolism is concerned. Materials and Methods This retrospective study was performed on 800 patients 152 males and 648 females of different socioeconomic background at secondary level regional referral hospital under Ministry of Health in Sultanate of Oman. The patients attending the outpatient clinic with various complaints and not responding to conventional treatment were advised for assessment of vitamin D [25 (OH D] level in blood. The patients were evaluated with general history, blood samples of serum calcium, phosphate, alkaline phosphatase and serum vitamin D level were measured by the most standardized laboratory of the country. Results Out of 800 patients, 275 cases had Vitamin D levels below 20 ng/ml and 167 patients had values greater than 30 ng/ml in serum.81% patients with vitamin D deficiency were females.56.25% patients were between third and sixth decade. Otolaryngologic manifestations were acute and recurrent URTI (n=352 44%. 7% of the patients presented with recurrent ear infection (otitis externa. The rest of them presented to a lesser extent with deafness, otosclerosis. Discussion Vitamin D deficiency has been reported worldwide as one of the commonest deficiency diseases. It can lead to autoimmune dysfunctions, Beta cell dysfunction in pancreas, Multiple sclerosis, recurrent chest infections and congestive cardiac failure. Studies have shown the involvement of cochlea with sensorineural hearing loss and otosclerosis. Conclusion Vitamin D deficiency has multi system implications as patients presenting with different signs and symptoms. Mass level screening and vitamin D

  7. Deficiencies of vitamins in CAPD patients: the effect of supplementation

    NARCIS (Netherlands)

    Boeschoten, E. W.; Schrijver, J.; Krediet, R. T.; Schreurs, W. H.; Arisz, L.

    1988-01-01

    Concentrations of the vitamins B1, B2, B6, B12, C, folic acid, A, E and beta-carotene were determined in blood and 24-h dialysate in 44 CAPD patients. Twenty-five of these patients were studied during chronic treatment (mean 313 days, range 60-1034 days). Nineteen patients were studied during

  8. Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2018-01-01

    Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

  9. Oral mucosal stem cells, human immature dental pulp stem cells and hair follicle bulge stem cells as adult stem cells able to correct limbal stem cell deficiency.

    Science.gov (United States)

    Hassan, Nada Tarek; AbdelAziz, Neveen Ahmed

    2018-02-23

    Adult stem cells are somatic stem cells distributed all over the body. They represent a promising future for regenera-tive medicine because of their multiple advantages as they are widely available, accessible, easily stored and manipulated to a wide range of cells and with minimal invasive extraction. This review describes three examples of adult stem cells: oral mucosal epithelial stem cells, human immature dental pulp stem cells and hair follicle bulge stem cells that show an ability to correct limbal stem cell deficiency, their isolation and cultivation methods, feeder layers, carriers, markers expressed, successfulness to regenerate the ocular surface and mimic the corneal function in LSCD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Psychiatric symptoms in a patient with isolated adrenocorticotropin deficiency: case report and literature review.

    Science.gov (United States)

    Morigaki, Yoko; Iga, Jun-Ichi; Kameoka, Naomi; Sumitani, Satsuki; Ohmori, Tetsuro

    2014-01-01

    We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Nutrient deficiencies in patients with obesity considering bariatric surgery: a cross-sectional study.

    Science.gov (United States)

    Lefebvre, Patrick; Letois, Flavie; Sultan, Ariane; Nocca, David; Mura, Thibaut; Galtier, Florence

    2014-01-01

    Nutritional deficiencies are common after bariatric surgery, but few studies have examined them preoperatively. The objective of this study was to evaluate several vitamins, nutrients, and nutritional markers and their determinants in patients with obesity considering bariatric surgery. Preoperative values of fasting plasma glucose, insulin, lipid profile, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, thyroid-stimulating hormone, calcium, phosphate, albumin, magnesium, total proteins, liver function tests, iron, ferritin, folate, vitamin A, vitamin B12, selenium, and zinc were evaluated in 267 Caucasian outpatients (74.2% women, aged 40.5±12.6 years) who were considering bariatric surgery. The determinants of nutrient variability were analyzed by linear regression for nutrients with a prevalence of deficiency>10%, i.e., serum 25(OH)D, iron, phosphate, magnesium, and vitamin A. Prevalence of inadequate concentrations was high for 25(OH)D (67.9% with values ≤ 20 ng/mL), magnesium (35.4%), phosphate (21.6%), iron (18.8%), and vitamin A (16.9%). Multiple deficiencies were common; 28.5%, 12.1%, and 6.3% of patients had 2, 3, and 4 deficiencies, respectively. In multivariate analyses, metabolic characteristics had an important impact on deficiencies, with lower values of 25(OH)D and vitamin A with increasing body mass index, lower values of 25(OH)D and magnesium with increasing fasting plasma glucose, and a positive correlation between vitamin A and triglycerides. Elevated TSH was associated with low iron concentrations. At all ages, micronutrient deficiencies were common, with high prevalence of concentration inadequacies for 25(OH)D, magnesium, phosphate, iron, and vitamin A. High body mass index and high fasting plasma glucose increased the risk of deficiencies, particularly for 25(OH)D. Preoperative screening and correction of deficiencies should be advised. © 2014 American Society for Bariatric Surgery Published by American Society for Metabolic and

  12. Ocular Surface Reconstruction with Cultivated Limbal Epithelial Cells in Limbal Stem Cell Deficiency: One-year Follow-up Results

    Directory of Open Access Journals (Sweden)

    İsmet Durak

    2012-05-01

    Full Text Available Pur po se: To evaluate the 1-year follow-up results of cultivated limbal epithelial cell (CLEC transplantation in unilateral limbal stem cell deficiency (LSCD. Ma te ri al and Met hod: One-year follow-up results of five unilateral LSCD patients who had undergone CLEC transplantation were evaluated. Parameters for this evaluation were: fluorescein staining of ocular surface, corneal vascularization and status of epithelium with slit lamp, and visual acuity. 1.5-mm limbal biopsy was performed from the superior limbus of the healthy eyes, broke into two equal pieces, expanded on human amniotic membrane (hAM and inserts for 14 days until getting 20 mm in size. CLECs on hAMs were used directly, and cells on inserts were usedafter detachment procedure. The symblepharon and pannus tissues were removed, superficial keratectomy was performed. CLEC on hAMs were transplanted with the epithelial side up onto the bare corneal stroma, sutured to the conjunctiva with 10-0 nylon sutures. Free CLEC layer from insert was placed on hAM as a second layer, additional hAM was used as a protective layer all over other tissues. Re sults: Median age was 44.4 years (14-71. The etiology was chemical burn in all patients. Median duration of symptoms was 10 years (2-18, median follow-up period was 12.6 (12-12.5 months. Preoperative best corrected visual acuities (BCVA were light perception in three patients, counting fingers at 50 cm in one patient and 3/10 in one patient. Visions were improved in all patients. Postoperative BCVA 12 months after the surgery were between counting fingers at 3 meters to 6/10. There was a temporary hemorrhage between the two layers of hAMs in one patient at the early postoperative period. Peripheral corneal vascularization has occurred in three patients, in patient corneal vascularization has reached to the paracentral area. Dis cus si on: CLEC transplantation is an efficient treatment option for unilateral LSCD in mid-long term. (Turk J

  13. Iron deficiency anemia as initial presentation of a non-small cell lung carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Philip V.M. Linsen

    2015-01-01

    Full Text Available Duodenal metastases secondary to lung cancer are very rare and most of the time asymptomatic. When symptomatic they usually present with bowel obstruction or perforation. We here describe the case of a 68 year-old man with a solitary metastasis in the duodenum from a non-small cell lung carcinoma (NSCLC. The patient presented with reduced exercise tolerance and iron deficiency anemia without clinical gastrointestinal blood loss. Further investigation showed a tumor in the left upper lung lobe and a duodenal metastasis for which he received chemotherapy. To the best of our knowledge this is the first case report of iron deficiency anemia as initial presentation of a duodenal metastasis from a NSCLC.

  14. The role of erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD) deficiency in the pathogenesis of anemia in patients on hemodialysis.

    Science.gov (United States)

    Ali, Elshazali Widaa; Ahmed, Emad Eldean Mohammed

    2013-11-01

    Anemia is a common feature among patients with chronic renal failure (CRF). Low activity of the erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD), which plays a major role in protecting red blood cells against oxidative agents, has been described as one of the contributing factors to anemia in patients with CRF treated with hemodialysis (HD). In this study, blood samples were randomly collected from 65 patients on HD and investigated for G6PD deficiency using the methemoglobin reduction test. The hemoglobin (Hb) concentration, packed cell volume (PCV), red blood cells (RBCs) count and reticulocyte count were determined in all the samples. Our results showed that 39 of 65 patients (60%) on HD had low G6PD activity and 26 (40%) patients had normal activity; 59% of the patients with low G6PD activity were males. The mean Hb, PCV and RBCs counts were lower in patients with low G6PD activity than in those with normal G6PD activity, but the difference was not statistically significant. Likewise, no statistically significant difference was found in the reticulocyte count in patients with low G6PD activity and in those with normal G6PD activity. The low G6PD activity that was found in a large proportion of patients on HD seems to be the result of enzyme inhibition rather than deficiency. No statistically significant difference was found in anemia parameters between patients with and without G6PD deficiency.

  15. The role of erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD deficiency in the pathogenesis of anemia in patients on hemodialysis

    Directory of Open Access Journals (Sweden)

    Elshazali Widaa Ali

    2013-01-01

    Full Text Available Anemia is a common feature among patients with chronic renal failure (CRF. Low activity of the erythrocyte enzyme glucose-6-phosphate dehydrogenase (G6PD, which plays a major role in protecting red blood cells against oxidative agents, has been described as one of the contributing factors to anemia in patients with CRF treated with hemodialysis (HD. In this study, blood samples were randomly collected from 65 patients on HD and investigated for G6PD deficiency using the methemoglobin reduction test. The hemoglobin (Hb concentration, packed cell volume (PCV, red blood cells (RBCs count and reticulocyte count were determined in all the samples. Our results showed that 39 of 65 patients (60% on HD had low G6PD activity and 26 (40% patients had normal activity; 59% of the patients with low G6PD activity were males. The mean Hb, PCV and RBCs counts were lower in patients with low G6PD activity than in those with normal G6PD activity, but the difference was not statistically significant. Likewise, no statistically significant difference was found in the reticulocyte count in patients with low G6PD activity and in those with normal G6PD activity. The low G6PD activity that was found in a large proportion of patients on HD seems to be the result of enzyme inhibition rather than deficiency. No statistically significant difference was found in anemia parameters between patients with and without G6PD deficiency.

  16. ATG7 deficiency suppresses apoptosis and cell death induced by lysosomal photodamage

    Science.gov (United States)

    Kessel, David H.; Price, Michael; Reiners, Jr., John J.

    2012-01-01

    Photodynamic therapy (PDT) involves photosensitizing agents that, in the presence of oxygen and light, initiate formation of cytotoxic reactive oxygen species (ROS). PDT commonly induces both apoptosis and autophagy. Previous studies with murine hepatoma 1c1c7 cells indicated that loss of autophagy-related protein 7 (ATG7) inhibited autophagy and enhanced the cytotoxicity of photosensitizers that mediate photodamage to mitochondria or the endoplasmic reticulum. In this study, we examined two photosensitizing agents that target lysosomes: the chlorin NPe6 and the palladium bacteriopheophorbide WST11. Irradiation of wild-type 1c1c7 cultures loaded with either photosensitizer induced apoptosis and autophagy, with a blockage of autophagic flux. An ATG7- or ATG5-deficiency suppressed the induction of autophagy in PDT protocols using either photosensitizer. Whereas ATG5-deficient cells were quantitatively similar to wild-type cultures in their response to NPe6 and WST11 PDT, an ATG7-deficiency suppressed the apoptotic response (as monitored by analyses of chromatin condensation and procaspase-3/7 activation) and increased the LD50 light dose by > 5-fold (as monitored by colony-forming assays). An ATG7-deficiency did not prevent immediate lysosomal photodamage, as indicated by loss of the lysosomal pH gradient. However, unlike wild-type and ATG5-deficient cells, the lysosomes of ATG7-deficient cells recovered this gradient within 4 h of irradiation, and never underwent permeabilization (monitored as release of endocytosed 10-kDa dextran polymers). We propose that the efficacy of lysosomal photosensitizers is in part due to both promotion of autophagic stress and suppression of autophagic prosurvival functions. In addition, an effect of ATG7 unrelated to autophagy appears to modulate lysosomal photodamage. PMID:22889762

  17. Vitamin and Mineral Deficiencies Are Highly Prevalent in Newly Diagnosed Celiac Disease Patients

    Directory of Open Access Journals (Sweden)

    Ad A. van Bodegraven

    2013-09-01

    Full Text Available Malabsorption, weight loss and vitamin/mineral-deficiencies characterize classical celiac disease (CD. This study aimed to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult CD-patients in the Netherlands. Newly diagnosed adult CD-patients were included (n = 80, 42.8 ± 15.1 years and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, B6, B12, and (25-hydroxy D, zinc, haemoglobin (Hb and ferritin were determined (before prescribing gluten free diet. Almost all CD-patients (87% had at least one value below the lower limit of reference. Specifically, for vitamin A, 7.5% of patients showed deficient levels, for vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32% had anaemia. Overall, 17% were malnourished (>10% undesired weight loss, 22% of the women were underweight (Body Mass Index (BMI 25. Vitamin deficiencies were barely seen in healthy controls, with the exception of vitamin B12. Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher grade of histological intestinal damage or (impaired nutritional status. In conclusion, vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.

  18. T cells exacerbate Lyme borreliosis in TLR2-deficient mice

    Directory of Open Access Journals (Sweden)

    Carrie E. Lasky

    2016-11-01

    Full Text Available Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as, arthritis, carditis and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via Toll-like receptor (TLR2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, while depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

  19. Cerebrospinal fluid hypocretin 1 deficiency, overweight, and metabolic dysregulation in patients with narcolepsy.

    Science.gov (United States)

    Heier, Mona S; Jansson, Tine S; Gautvik, Kaare M

    2011-12-15

    The possible relationship between cerebrospinal fluid (CSF) hypocretin and leptin levels, overweight, and association to risk factors for diabetes 2 in narcolepsy with cataplexy were compared to patients with idiopathic hypersomnia and controls. 26 patients with narcolepsy, cataplexy, and hypocretin deficiency; 23 patients with narcolepsy, cataplexy, and normal hypocretin values; 11 patients with idiopathic hypersomnia; and 43 controls. Body mass index (BMI), serum leptin, and HbA1C were measured in patients and controls; and CSF hypocretin 1 and leptin measured in all patients. Female and male patients with narcolepsy and hypocretin deficiency had the highest mean BMI (27.8 and 26.2, respectively), not statistically different from patients with narcolepsy and normal hypocretin or controls, but statistically higher than the patients with idiopathic hypersomnia (p 30) was increased in both narcolepsy groups. Serum and CSF leptin levels correlated positively to BMI in patients and controls, but not to CSF hypocretin concentrations. HbA1C was within normal levels and similar in all groups. The study confirms a moderate tendency to obesity (BMI > 30) and overweight in patients with narcolepsy and cataplexy. Obesity was not correlated to hypocretin deficiency or reduced serum or CSF leptin concentrations. We suggest that overweight and possible metabolic changes previously reported in narcolepsy, may be caused by other mechanisms.

  20. Absolute and Functional Iron Deficiency Anemia among Different Tumors in Cancer Patients in South Part of Iran, 2014

    Science.gov (United States)

    Hashemi, Seyed Mehdi; Mashhadi, Mohammad Ali; Mohammadi, Mehdi; Ebrahimi, Maryam; Allahyari, Abolghasem

    2017-01-01

    Background: Anemia is a common problem in cancer patients. This study aimed to investigate the frequency rate of absolute and functional iron deficiency anemia among different tumors and its distribution in different stages of cancer in solid tumors. Materials and Methods: This study was performed on 597 patients with cancer referred to Ali-Ebne-Abitaleb Hospital in Zahedan. Laboratory tests included serum iron, transferrin saturation, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count (CBC). The malignancy type and stages were recorded. Data were analysed using SPSS statistics software (Ver.19). Results: Four hundred and fifty-seven patients (76.5 %) diagnosed with solid tumors and 140 (23.5%) suffered from hematologic malignancies. Among patients with solid tumors, functional iron deficiency had the highest rate (300 patients had anemia and 243 (53.2%) of whom were functionally iron deficient), but in hematologic malignancies most of patients had not iron deficiency (66 patients had not iron deficiency against 12 patients had absolute iron deficiency and 62 patients had functional iron deficiency anemia) (P-value=0.021). No significant differences were observed among the various stages of cancers in terms of degrees of iron deficiency (P>0.05). Conclusion: The results of the study showed that solid tumors had a higher rate of absolute and functional iron deficiency anemia, compared to hematologic malignancies. But there was no difference between the different stages of the disease. PMID:28989585

  1. Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Anna-Kaisa Niemi

    2014-01-01

    Full Text Available The pathophysiology of succinic semialdehyde dehydrogenase (SSADH deficiency is not completely understood. Oxidative stress, mitochondrial pathology, and low reduced glutathione levels have been demonstrated in mice, but no studies have been reported in humans. We report on a patient with SSADH deficiency in whom we found low levels of blood reduced glutathione (GSH, and elevations of dicarboxylic acids in urine, suggestive of possible redox imbalance and/or mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a potential therapeutic approach if our findings are confirmed in other patients.

  2. Selective IgM Deficiency: Clinical and Laboratory Features of 17 Patients and a Review of the Literature.

    Science.gov (United States)

    Chovancova, Zita; Kralickova, Pavlina; Pejchalova, Alena; Bloomfield, Marketa; Nechvatalova, Jana; Vlkova, Marcela; Litzman, Jiri

    2017-08-01

    Primary selective IgM deficiency (sIgMD) is a primary immunodeficiency with unclear pathogenesis and a low number of published cases. We reviewed clinical and laboratory manifestations of 17 sIgMD patients. Serum IgM, IgG, and its subclasses, IgA, IgE, antibodies against tetanus toxoid, pneumococcal polysaccharides and Haemophilus influenzae type b, isohemagglutinins, and T and B lymphocyte subsets, expressions of IgM on B cells and B lymphocyte production of IgM were compared with previously reported case reports and a small series of patients, which included 81 subjects in total. We found that some patients in our cohort (OC) and published cases (PC) had increased IgE levels (OC 7/15; PC 21/37), decreased IgG4 levels (OC 5/14), very low titers of isohemagglutinins (OC 8/8; PC 18/21), increased transitional B cell counts (OC 8/9), decreased marginal zone B cell counts (OC 8/9), and increased 21 low B cell counts (OC 7/9). Compared with the PC (20/20), only two of five OC patients showed very low or undetectable production of IgM after stimulation. A majority of the patients had normal antibody production to protein and polysaccharide antigens, basic lymphocyte subset counts, and expression of surface IgM molecules on B cells. Low IgM levels are associated with various immunopathological disorders; however, pathogenic mechanisms leading to decreased IgM serum level in selective IgM deficiency remain unclear. Moreover, it is difficult to elucidate how strong these associations are and if these immunopathological conditions are primary or secondary.

  3. Differential programming of p53-deficient embryonic cells during rotenone block

    Science.gov (United States)

    Mitochondrial dysfunction has been implicated in chemical toxicities. The present study used an in vitro model to investigate the differential expression of metabolic pathways during cellular stress in p53- efficient embryonic fibroblasts compared to p53-deficient cells. These c...

  4. Maternal vitamin B12 deficiency and abnormal cell-free DNA results in pregnancy

    NARCIS (Netherlands)

    Schuring-Blom, Heleen; Lichtenbelt, Klaske; van Galen, Karin; Elferink, Martin; Weiss, Marjan; Vermeesch, Joris Robert; Page-Christiaens, Lieve

    2016-01-01

    What's Already Known about this Topic? Prenatal testing with cell-free DNA may incidentally identify maternal genetic anomalies and malignancies. What does this Study Add? Profound vitamin B12 deficiency with intramedullary hemolysis may cause abnormal genomic patterns that can be detected by

  5. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin

    Energy Technology Data Exchange (ETDEWEB)

    Oommen, Deepu [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom); Yiannakis, Dennis [Plymouth Oncology Centre, Derriford Hospital, Plymouth Hospitals NHS Trust, Plymouth PL6 8DH (United Kingdom); Jha, Awadhesh N., E-mail: a.jha@plymouth.ac.uk [School of Biological Sciences, Plymouth University, Plymouth PL4 8AA (United Kingdom)

    2016-02-15

    Highlights: • BRCA1 deficient cancer cells exhibit increased DNA damage upon auranofin treatment. • Auranofin induces apoptosis in BRCA1 deficient cancer cells despite the activation of Nrf2. • Antioxidant protects BRCA1 deficient cancer cells from auranofin. - Abstract: Auranofin, a thioredoxin reductase inhibitor and an anti-rheumatic drug is currently undergoing phase 2 clinical studies for repurposing to treat recurrent epithelial ovarian cancer. Previous studies have established that auranofin exerts its cytotoxic activity by increasing the production of reactive oxygen species (ROS). Breast cancer 1, early onset (BRCA1) is a DNA repair protein whose functional status is critical in the prognosis of ovarian cancer. Apart from its key role in DNA repair, BRCA1 is also known to modulate cellular redox homeostasis by regulating the stability of anti-oxidant transcription factor, nuclear factor erythroid 2—related factor 2 (Nrf2) via direct protein–protein interaction. However, it is currently unknown whether BRCA1 modulates the sensitivity of ovarian cancer cells to auranofin. Here we report that BRCA1-depleted cells exhibited increased DNA double strand breaks (DSBs) and decreased clonogenic cell survival upon auranofin treatment. Interestingly, auranofin induced the expression of Nrf2 in BRCA1-depleted cells suggesting its regulation independent of BRCA1. Furthermore, anti-oxidant agent, N-acetyl cysteine (NAC) protected BRCA1-depleted cells from DNA damage and apoptosis induced by auranofin. Our study suggests that accumulated lethal DSBs resulting from the oxidative damage render BRCA1 deficient cells more sensitive to auranofin despite the activation of Nrf2.

  6. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities.

    Science.gov (United States)

    Soheili, Habib; Abolhassani, Hassan; Arandi, Narges; Khazaei, Hossein Ali; Shahinpour, Shervin; Hirbod-Mobarakeh, Armin; Rezaei, Nima; Aghamohammadi, Asghar

    2013-01-01

    Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25(high)forkhead box P3 (FoxP3)+ regulatory T cells (T(reg)) have been shown in association with autoimmune and inflammatory disorders. In order to evaluate the relationship between autoimmunity and T(reg) in SIgAD, we studied 26 IgA-deficient patients (aged 4-17 years) with serum IgA levels 2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). This study showed decreased proportions of T(reg) in SIgAD patients, particularly in those with signs of chronic inflammation. Copyright © 2012 S. Karger AG, Basel.

  7. Critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with microcytic anemia.

    Science.gov (United States)

    Urrechaga, Eloísa; Hoffmann, Johannes J M L

    2017-08-28

    Many discriminant formulas have been reported for distinguishing thalassemia trait from iron deficiency in patients with microcytic anemia. Independent verification of several discriminant formulas is deficient or even lacking. Therefore, we have retrospectively investigated discriminant formulas in a large, well-characterized patient population. The investigational population consisted of 2664 patients with microcytic anemia: 1259 had iron deficiency, 1196 'pure' thalassemia trait (877 β- and 319 α-thalassemia), 150 had thalassemia trait with concomitant iron deficiency or anemia of chronic disease, and 36 had other diseases. We investigated 25 discriminant formulas that only use hematologic parameters available on all analyzers; formulas with more advanced parameters were disregarded. The diagnostic performance was investigated using ROC analysis. The three best performing formulas were the Jayabose (RDW index), Janel (11T), and Green and King formulas. The differences between them were not statistically significant (p>0.333), but each of them had significantly higher area under the ROC curve than any other formula. The Jayabose and Green and King formulas had the highest sensitivities: 0.917 both. The highest specificity, 0.925, was found for the Janel formula, which is a composite score of 11 other formulas. All investigated formulas performed significantly better in distinguishing β- than α-thalassemia from iron deficiency. In our patient population, the Jayabose RDW index, the Green and King formula and the Janel 11T score are superior to all other formulas examined for distinguishing between thalassemia trait and iron deficiency anemia. We confirmed that all formulas perform much better in β- than in α-thalassemia carriers and also that they incorrectly classify approximately 30% of thalassemia carriers with concomitant other anemia as not having thalassemia. The diagnostic performance of even the best formulas is not high enough for making a final

  8. Proteomics reveals reduced expression of tansketolase in pyrimidine 5'-nucleotidase deficient patients

    NARCIS (Netherlands)

    Barasa, Benjamim; van Oirschot - Hermans, B.A.; Bianchi, P.; van Solinge, WW; Heck, Albert J R; van Wijk, HA; Slijper, M.

    Purpose To date, it remains a challenge to correctly and timely diagnose red blood cell (RBC) enzymopathies that result in hereditary nonspherocytic hemolytic anemia (HNSHA), the third most common of which is pyrimidine 5′-nucleotidase (P5N) deficiency with just over 100 cases recognized and

  9. Increased numbers of spleen colony forming units in B cell deficient CBA/N mice

    International Nuclear Information System (INIS)

    Wiktor-Jedrzejczak, W.; Krupienicz, A.; Scher, I.

    1986-01-01

    The formation of exogenous and endogenous spleen colonies was studied in immune-defective mice expressing the CBA/N X-linked xid gene. Bone marrow and spleen cells of immune deficient mice formed increased numbers of eight-day exogenous spleen colonies when transferred to either normal or B cell deficient lethally irradiated recipients. Moreover, defective mice showed increased formation of five-day endogenous spleen colonies (derived from transient endogenous colony forming units; T-CFU) and of ten-day endogenous spleen colonies (derived from CFU-S). Among the possible mechanisms responsible for the observed effects, the most probable appears the one in which decreased numbers of B cell precursors stimulate stem cell pools through a feedback mechanism. (orig.) [de

  10. Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease?

    Science.gov (United States)

    Albayrak, Canan; Albayrak, Davut

    2015-03-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

  11. Ionizing radiation sensitivity of DNA polymerase lambda-deficient cells.

    NARCIS (Netherlands)

    Vermeulen, C.; Bertocci, B.; Begg, A.C.; Vens, C.

    2007-01-01

    Ionizing radiation induces a diverse spectrum of DNA lesions, including strand breaks and oxidized bases. In mammalian cells, ionizing radiation-induced lesions are targets of non-homologous end joining, homologous recombination, and base excision repair. In vitro assays show a potential involvement

  12. Development of a human mitochondrial oligonucleotide microarray (h-MitoArray) and gene expression analysis of fibroblast cell lines from 13 patients with isolated F1Fo ATP synthase deficiency

    Czech Academy of Sciences Publication Activity Database

    Čížková, Alena; Stránecký, V.; Ivánek, Robert; Hartmannová, H.; Nosková, L.; Piherová, L.; Tesařová, M.; Hansíková, H.; Honzík, T.; Zeman, J.; Divina, Petr; Potocká, A.; Paul, J.; Sperl, W.; Mayr, J. A.; Seneca, S.; Houštěk, J.; Kmoch, S.

    2008-01-01

    Roč. 9, - (2008), s. 38-38 ISSN 1471-2164 R&D Projects: GA ČR(CZ) GD303/03/H065; GA ČR(CZ) GA303/07/0781 Grant - others:GA MZd(CZ) NR8069 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514 Keywords : microarray * mitochondria * F1Fo ATP synthase deficiency Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.926, year: 2008

  13. High prevalence of immunoglobulin A deficiency in patients with type 1 diabetes mellitus detected by ELISA

    OpenAIRE

    Loraine Farias Landgraf; Nelson Augusto Rosário; Juliana Ferreira de Moura; Katherine Andrew Wells; Bonald Cavalcanti Figueiredo

    2008-01-01

    Objective: To measure serum levels of immunoglobulin A byimmunoenzymatic assay (ELISA) in type 1 diabetes mellitus (DM-1)patients and to verify the prevalence of immunoglobulin A deficiency(IgAD) in diabetic patients. Methods: The serum immunoglobulin Alevel was determined in 149 DM-1 patients by three methods. IgADwas defined as serum immunoglobulin A level lower than 5 mg/dl.If serum immunoglobulin A level was undetectable by turbidimetry,radial immunodiffusion was performed in low plate co...

  14. Lupus vulgaris in a patient with systemic lupus erythematosus and persistent IgG deficiency.

    Science.gov (United States)

    Düzgün, N; Duman, M; Sonel, B; Peksari, Y; Erdem, C; Tokgöz, G

    1997-01-01

    We present the case of a patient with juvenile onset systemic lupus erythematosus (SLE) who developed a persistent, acquired hypogammaglobulinaemia with IgG deficiency. The hypogammaglobulinaemia was probably a complication of high dose corticosteroid treatment. The serum IgG level remained subnormal despite intravenous immunoglobulin therapy. Lupus vulgaris, which developed on the nasal cartilage in this patient with SLE, is not an expected finding. This patient is probably the first reported case of SLE associated with lupus vulgaris.

  15. Oral and Dental Health Status in Patients with Primary Antibody Deficiencies

    OpenAIRE

    Ghasem Meighani; Asghar Aghamohammadi; Honarmand Javanbakht; Hassan Abolhassani; Sina Nikayin; Seyed Mehryar Jafari; Mehdi Ghandehari Motlagh; Ahmad Reza Shamshiri; Nima Rezaei

    2011-01-01

    Primary antibody deficiencies (PAD) are a group of immune system disorders, associated with decreased levels of secretory and protective immunoglobulins. Because of the important role of immunoglobulins in the protection  of oral cavity, patients with PADs  are more susceptible to dental caries or oral manifestations.This study was performed  to investigate the oral and dental manifestations of PADs patients. In this study, 33 patients with PADs (21 common variable immunodeficiency, 8 X- link...

  16. Metaxin deficiency alters mitochondrial membrane permeability and leads to resistance to TNF-induced cell killing.

    Science.gov (United States)

    Ono, Koh; Wang, Xiaofei; Kim, Sung Ouk; Armstrong, Lucas C; Bornstein, Paul; Han, Jiahuai

    2010-02-01

    Metaxin, a mitochondrial outer membrane protein, is critical for TNF-induced cell death in L929 cells. Its deficiency, caused by retroviral insertion-mediated mutagenesis, renders L929 cells resistance to TNF killing. In this study, we further characterized metaxin deficiency-caused TNF resistance in parallel with Bcl-X(L) overexpression-mediated death resistance. We did not find obvious change in mitochondria membrane potential in metaxin-deficient (Met(mut)) and Bcl-X(L)-overexpressing cells, but we did find an increase in the release rate of the mitochondrial membrane potential probe rhodamine 123 (Rh123) that was preloaded into mitochondria. In addition, overexpression of a function-interfering mutant of metaxin (MetaΔTM/C) or Bcl-X(L) in MCF-7.3.28 cells also resulted in an acquired resistance to TNF killing and a faster rate of Rh123 release, indicating a close correlation between TNF resistance and higher rates of the dye release from the mitochondria. The release of Rh123 can be controlled by the mitochondrial membrane permeability transition (PT) pore, as targeting an inner membrane component of the PT pore by cyclosporin A (CsA) inhibited Rh123 release. However, metaxin deficiency and Bcl-X(L) overexpression apparently affect Rh123 release from a site(s) different from that of CsA, as CsA can overcome their effect. Though both metaxin and Bcl-X(L) appear to function on the outer mitochondrial membrane, they do not interact with each other. They may use different mechanisms to increase the permeability of Rh123, since previous studies have suggested that metaxin may influence certain outer membrane porins while Bcl-X(L) may form pores on the outer membrane. The alteration of the mitochondrial outer membrane properties by metaxin deficiency and Bcl-X(L) overexpression, as indicated by a quicker Rh123 release, may be helpful in maintaining mitochondrial integrity.

  17. [TOTAL PARENTERAL NUTRITION IN A PREGNANT PATIENT WITH ACUTE PANCREATITIS AND LIPOPROTEIN LIPASE DEFICIENCY].

    Science.gov (United States)

    Contreras-Bolívar, Victoria; González-Molero, Inmaculada; Valdivieso, Pedro; Olveira, Gabriel

    2015-10-01

    We present a case of severe acute pancreatitis induced by hypertriglyceridemia secondary to lipoprotein lipase (LPL) deficiency in a pregnant patient with gestational diabetes, initially maneged with diet but it was later necessary to carry out artificial nutricional support measures: total parenteral nutrition. LPL deficiency might cause severe hypertriglyceridemia, repetition acute pancreatitis which is an unwieldy and severe situation during pregnancy. Acute familial hypertriglyceridemia pancreatitis accounts for 5% of cases, including LPL deficiency. The goal of treatment is to reach triglycerides levels below 500 mg/dl, being very low fat diet the treatment of choice, drugs or plasmapheresis techniques can also be associated. TPN enriched in ω3 fatty acids and glutamine was safe and effective in our patient with significant decrease in triglyceride levels. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  18. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    . Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...... variables were analysed in relation to cataplexy and hypocretin deficiency with uni- and multivariate logistic/linear regression models, controlling for possible rapid eye movement sleep behaviour disorder biasing factors (age, gender, disease duration, previous anti-cataplexy medication). Only hypocretin...

  19. Protection of Human Neutrophils by Endogenous Catalase: STUDIES WITH CELLS FROM CATALASE-DEFICIENT INDIVIDUALS

    OpenAIRE

    Roos, Dirk; Weening, Ron S.; Wyss, Sonja R.; Aebi, Hugo E.

    1980-01-01

    To investigate the importance of catalase as a protecting enzyme against oxidative damage in phagocytic leukocytes, we have tested the functional capacity of neutrophils from two individuals homozygous for Swiss-type acatalasemia and from two individuals heterozygous for this deficiency. In the former cells, 25-30% of residual activity of catalase was present. In the latter cells, the values were close to normal.

  20. Root graviresponsiveness and columella cell structure in carotenoid-deficient seedlings of Zea mays

    Science.gov (United States)

    Moore, R.; McClelen, C. E.

    1985-01-01

    Root graviresponsiveness in normal and carotenoid-deficient mutant seedlings of Zea mays was not significantly different. Columella cells in roots of mutant seedlings were characterized by fewer, smaller, and a reduced relative volume of plastids as compared to columella cells of normal seedlings. Plastids in columella cells of mutant seedlings possessed reduced amounts of starch. Although approximately 10 per cent of the columella cells in mutant seedlings lacked starch, their plastids were located at the bottom of the cell. These results suggest that (i) carotenoids are not necessary for root gravitropism, (ii) graviresponsiveness is not necessarily proportional to the size, number, or relative volume of plastids in columella cells, and (iii) sedimentation of plastids in columella cells may not result directly from their increased density due to starch content. Plastids in columella cells of normal and mutant seedlings were associated with bands of microtubule-like structures, suggesting that these structures may be involved in 'positioning' plastids in the cell.

  1. Nutritional deficiency of post-bariatric surgery body contouring patients: what every plastic surgeon should know.

    Science.gov (United States)

    Agha-Mohammadi, Siamak; Hurwitz, Dennis J

    2008-08-01

    Bariatric surgery, particularly the Roux-en-Y gastric bypass, is currently the most effective method of sustainable weight loss for the morbidly obese patient population. Unfortunately, the nutritional adequacy of the postoperative diet has frequently been overlooked, and in the months to years that follow, many nutritional deficiencies have become apparent. Furthermore, once weight loss has reached a plateau, many patients become candidates for body contouring surgery and other aesthetic operations. The aim of this review was to highlight the nutritional deficiencies of post-bariatric surgery patients as related to planned body contouring surgery. This review was prepared by an extensive search of the bariatric surgery literature. The current data indicate that many post-bariatric surgery patients have protein-calorie malnutrition as well as various vitamins and mineral deficiencies that may limit optimal health and healing. It is essential that those plastic surgeons who treat post-bariatric surgery patients are aware of these nutritional deficiencies, which can be minimized by adhering to eating guidelines and supplemental prescriptions. Although there are many studies documenting relationships between malnutrition and poor wound healing, the optimal nutrient intake in the post-bariatric surgery state to promote wound healing is unknown. It is, however, clear that proteins, vitamin A, vitamin C, arginine, glutamine, zinc, and selenium have significant beneficial effects on wound healing and optimizing the immune system.

  2. Prevalence of Vitamin D Deficiency and Its Association With Metabolic Disease in Korean Orthopedic Patients.

    Science.gov (United States)

    Kim, Ki-Tack; Kang, Kyung-Chung; Shin, Dong-Eun; Lee, Sang-Hoon; Lee, Jung-Hee; Kwon, Tae-Yoon

    2015-10-01

    Vitamin D is considered essential for bone and muscle health, and some studies have demonstrated the positive effects of vitamin D on metabolic diseases and cancer. Nevertheless, a high prevalence of vitamin D deficiency has been reported in various populations, regardless of country or race. However, no studies regarding the prevalence of vitamin D deficiency in Korean orthopedic patients currently exist. This cross-sectional study included 272 male and 937 female patients aged 50 years and older who were consecutively admitted to the authors' orthopedic department. Vitamin D (25-hydroxy vitamin D), bone turnover markers (osteocalcin, c-telopeptide), and bone mineral density were measured. The prevalence of vitamin D deficiency and its association with other factors were evaluated. Mean patient age was 67.2 ± 8.9 years, and mean level of vitamin D was 16.1 ± 9.1 ng/mL. Overall, 91.2% of patients had deficient (orthopedic patients of this region was extremely low, regardless of sex and age. Although vitamin D was not directly associated with bone mineral density, there were significant associations between vitamin D and other factors related to bone health and metabolic diseases. Copyright 2015, SLACK Incorporated.

  3. Higher infection of dengue virus serotype 2 in human monocytes of patients with G6PD deficiency.

    Directory of Open Access Journals (Sweden)

    Yuan-Chang Chao

    Full Text Available The prevalence of glucose-6-phosphate dehydrogenase (G6PD deficiency is high in Asia. An ex vivo study was conducted to elucidate the association of G6PD deficiency and dengue virus (DENV infection when many Asian countries are hyper-endemic. Human monocytes from peripheral mononuclear cells collected from 12 G6PD-deficient patients and 24 age-matched controls were infected with one of two DENV serotype 2 (DENV-2 strains-the New Guinea C strain (from a case of dengue fever or the 16681 strain (from a case of dengue hemorrhagic fever with a multiplicity of infection of 0.1. The infectivity of DENV-2 in human monocytes was analyzed by flow cytometry. Experimental results indicated that the monocytes of G6PD-deficient patients exhibited a greater levels of infection with DENV-2 New Guinea C strain than did those in healthy controls [mean+/-SD:33.6%+/-3.5 (27.2% approximately 39.2% vs 20.3%+/-6.2 (8.0% approximately 30.4%, P<0.01]. Similar observations were made of infection with the DENV-2 16681 strain [40.9%+/-3.9 (35.1% approximately 48.9% vs 27.4%+/-7.1 (12.3% approximately 37.1%, P<0.01]. To our knowledge, this study demonstrates for the first time higher infection of human monocytes in G6PD patients with the dengue virus, which may be important in increasing epidemiological transmission and perhaps with the potential to develop more severe cases pathogenically.

  4. Vitamin D deficiency in patients with cutaneous lupus erythematosus is prevalent throughout the year.

    Science.gov (United States)

    Heine, G; Lahl, A; Müller, C; Worm, M

    2010-10-01

    Vitamin D mediates immunomodulatory functions and its deficiency has been associated with an increased prevalence of immunological diseases including systemic lupus erythematosus (SLE). Chronic discoid or subacute cutaneous lupus erythematosus (CLE) are ultraviolet (UV)-triggered skin diseases. As vitamin D is mostly UV-derived and not from nutrition, its deficiency is frequent especially during the UV-deprived winter months. To compare the vitamin D status of patients with CLE with patients with type I allergy and healthy individuals during the summer or winter months. The vitamin D status of patients with CLE (n = 41) was compared with patients with type I allergy (n = 24), healthy individuals (n = 25) and a reference pool (n = 1951) by means of concentrations of circulating storage metabolite 25-hydroxyvitamin D in the summer and winter. Serum 25-hydroxyvitamin D concentrations were lower during the winter in the reference population, and type I allergic and healthy individuals (29.2–35.5 nmol L)1) compared with the summer months (56.3–89.8 nmol L)1) and paralleled by the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D< 50 nmol L)1; winter: 70.8–73.4%, summer: 34.9–39.4%). In contrast, vitamin D deficiency in patients with CLE was prevalent throughout the year (summer: 85.7%,winter: 97.1%). In patients with CLE with concomitant prednisolone treatment, the 25-hydroxyvitamin D serum levels were comparable with (mean daily intake 877 IU) or without vitamin D supplementation during summer or winter (P = 0.75 and P = 0.14, respectively). Our data identify vitamin D deficiency in patients with CLE throughout the year and indicate that monitoring and correcting the vitamin D status should be considered to prevent bone demineralization and fractures and to modulate beneficially immunological dysfunction.

  5. Automatic analysis of image of surface structure of cell wall-deficient EVC.

    Science.gov (United States)

    Li, S; Hu, K; Cai, N; Su, W; Xiong, H; Lou, Z; Lin, T; Hu, Y

    2001-01-01

    Some computer applications for cell characterization in medicine and biology, such as analysis of surface structure of cell wall-deficient EVC (El Tor Vibrio of Cholera), operate with cell samples taken from very small areas of interest. In order to perform texture characterization in such an application, only a few texture operators can be employed: the operators should be insensitive to noise and image distortion and be reliable in order to estimate texture quality from images. Therefore, we introduce wavelet theory and mathematical morphology to analyse the cellular surface micro-area image obtained by SEM (Scanning Electron Microscope). In order to describe the quality of surface structure of cell wall-deficient EVC, we propose a fully automatic computerized method. The image analysis process is carried out in two steps. In the first, we decompose the given image by dyadic wavelet transform and form an image approximation with higher resolution, by doing so, we perform edge detection of given images efficiently. In the second, we introduce many operations of mathematical morphology to obtain morphological quantitative parameters of surface structure of cell wall-deficient EVC. The obtained results prove that the method can eliminate noise, detect the edge and extract the feature parameters validly. In this work, we have built automatic analytic software named "EVC.CELL".

  6. Mismatch repair deficiency in Lynch syndrome-associated colorectal adenomas is more prevalent in older patients.

    Science.gov (United States)

    Tanaka, Masahiro; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Taniguchi, Hirokazu; Kanemitsu, Yukihide; Nagino, Masato; Sekine, Shigeki

    2016-08-01

    The aim of this study was to examine the expression of mismatch repair (MMR) proteins in Lynch syndrome (LS)-associated colorectal adenomas and to evaluate their relationship with clinicopathological variables and potential utility in LS screening. We performed immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 in 134 adenomas obtained from 26 genetically confirmed LS patients. MMR deficiency, as determined by loss of any MMR protein, was observed in 113 adenomas (84%). All the MMR-deficient adenomas exhibited homogeneous loss of MMR proteins, which reflected underlying germline mutations. MMR deficiency was more frequent in adenomas obtained from older patients (aged ≥60 years; 81 of 86, 94%), with larger tumour size (>5 mm; 71 of 73, 97%) and with high-grade dysplasia (50 of 51, 98%). Multivariate analyses indicated that increased age and larger tumour size were associated independently with MMR deficiency. This study shows that MMR deficiency is associated significantly with increased age, in addition to two previously reported factors-larger size and high-grade dysplasia. When adenomas are analysed during LS screening, high sensitivity is expected if the adenomas are associated with any of these three factors. © 2016 John Wiley & Sons Ltd.

  7. Factor VII Deficiency: From Basics to Clinical Laboratory Diagnosis and Patient Management.

    Science.gov (United States)

    Sevenet, Pierre-Olivier; Kaczor, Daniel A; Depasse, Francois

    2017-10-01

    Factor VII (FVII) deficiency is a rare inheritable bleeding disorder affecting 1/500 000 individuals. Clinical manifestations are heterogeneous, from asymptomatic to severe and potentially fatal bleeding. These clinical manifestations do not correlate well with FVII plasma levels. For this reason, FVII-deficient patient management during surgery or for long-term prophylaxis remains challenging. Laboratory testing for FVII activity is, however, the first-line method for FVII deficiency diagnosis and is helpful for managing patients in combination with clinical history. Additional testing consists of FVII immunoassay and genetic testing. Genetic abnormalities on the FVII gene are heterogeneous and can translate into quantitative or qualitative defects. Some of the latter can react differently with different thromboplastins; this can be misleading for the laboratory as no consensus exists at present on an FVII deficiency diagnosis methodology. Indeed, no single test is able to predict accurately the bleeding risk. This review provides a broad picture of inherited and acquired FVII deficiency with a particular focus on laboratory diagnosis.

  8. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group

    DEFF Research Database (Denmark)

    Attanasio, A F; Lamberts, S W; Matranga, A M

    1997-01-01

    The onset of adult GH deficiency may be during either adulthood (AO) or childhood (CO), but potential differences have not previously been examined. In this study the baseline and GH therapy (12.5 micrograms/kg per day) data from CO (n = 74; mean age 29 yr) and AO (n = 99; mean age 44 yr) GH......-deficient adult patients have been compared. The first 6 months comprised randomized, double-blind treatment with GH or placebo, then all patients were GH-treated for a further 12 months. At baseline the height, body weight, body mass index, lean body mass, and waist/hip ratio of AO patients were significantly (P...

  9. [Neonatal screening of hemoglobinopathies and G6PD deficiency in Catalonia (Spain). Molecular study of sickle cell disease associated with alpha thalassemia and G6PD deficiency].

    Science.gov (United States)

    Mañú Pereira, María Del Mar; Cabot, Anna; Martínez González, Ana; Sitjà Navarro, Eulalia; Cararach, Vicent; Sabrià, Josep; Boixaderas, Jordi; Teixidor, Roser; Bosch, Albert; López Vílchez, M Angeles; Martín Ibáñez, Itziar; Carrión, Teresa; Plaja, Pere; Sánchez, Mario; Vives Corrons, José Luis

    2007-06-30

    The prevalence of hemoglobinopathies and glucose-6-phosphate dehidrogenase (G6PD) deficiency in the Catalan neonatal population is increasing due to immigration. Coinheritance of more than a single RBC genetic defect is becoming more frequent and diagnostic pitfalls are also increasing. We intended to demonstrate the need to perform an early diagnosis of sickle cell disease (SCD) by means of neonatal screening, to establish the prevalence of SCD associated with alpha thalassemia and G6PD deficiency and to identify genotypes associated with sickle cell disease and G6PD deficiency. 4,020 blood samples from newborns were screened. For the screening of hemoglobinopathies the high performance liquid chromatography method was used and for G6PD deficiency the fluorescent spot test was employed. We studied the association between betaS gene and alpha thalassaemia del-3.7 Kb. SCD and G6PD deficiency genotypes were established. Prevalence of SCD in population at risk was 1/475 newborns. Prevalence of G6PD deficiency in population at risk was 1/43, and in autochthonous population was 1/527 newborns. In all the cases, sickle hemoglobin was confirmed by ARMS (amplification refractory mutation system). Association between betaS gene and alpha thalassaemia del-3.7 Kb was found in 32.2% of the samples, and an association between betaS gene and G6PD deficiency was observed in 7% of the samples. This study confirms the high prevalence of SCD and G6PD deficiency in population at risk as well as their genetic and clinical heterogeneity. The study of genotype/phenotype relationships allows a better knowledge of molecular mechanism and is useful to establish suitable criteria of diagnosis.

  10. Chk1 suppresses bypass of mitosis and tetraploidization in p53-deficient cancer cells.

    Science.gov (United States)

    Wilsker, Deborah; Chung, Jon H; Bunz, Fred

    2012-04-15

    Many cancer cells are unable to maintain a numerically stable chromosome complement. It is well established that aberrant cell division can generate progeny with increased ploidy, but the genetic factors required for maintenance of diploidy are not well understood. Using an isogenic model system derived by gene targeting, we examined the role of Chk1 in p53-proficient and -deficient cancer cells. Targeted inactivation of a single CHK1 allele in stably diploid cells caused an elevated frequency of mitotic bypass if p53 was naturally mutated or experimentally disrupted by homologous recombination. CHK1-haploinsufficient, p53-deficient cells frequently underwent sequential rounds of DNA synthesis without an intervening mitosis. These aberrant cell cycles resulted in whole-genome endoreduplication and tetraploidization. The unscheduled bypass of mitosis could be suppressed by targeted reversion of a p53 mutation or by exogenous expression of Cdk1. In contrast, the number of tetraploid cells was not increased in isogenic cell populations that harbor hypomorphic ATR mutations, suggesting that suppression of unscheduled mitotic bypass is a distinct function of Chk1. These results are consistent with a recently described role for Chk1 in promoting the expression of genes that promote cell cycle transitions and demonstrate how Chk1 might prevent tetraploidization during the cancer cell cycle.

  11. Defective bone repair in mast cell-deficient Cpa3Cre/+ mice.

    Directory of Open Access Journals (Sweden)

    Jose Luis Ramirez-GarciaLuna

    Full Text Available In the adult skeleton, cells of the immune system interact with those of the skeleton during all phases of bone repair to influence the outcome. Mast cells are immune cells best known for their pathologic role in allergy, and may be involved in chronic inflammatory and fibrotic disorders. Potential roles for mast cells in tissue homeostasis, vascularization and repair remain enigmatic. Previous studies in combined mast cell- and Kit-deficient KitW-sh/W-sh mice (KitW-sh implicated mast cells in bone repair but KitW-sh mice suffer from additional Kit-dependent hematopoietic and non- hematopoietic deficiencies that could have confounded the outcome. The goal of the current study was to compare bone repair in normal wild type (WT and Cpa3Cre/+ mice, which lack mast cells in the absence of any other hematopoietic or non- hematopoietic deficiencies. Repair of a femoral window defect was characterized using micro CT imaging and histological analyses from the early inflammatory phase, through soft and hard callus formation, and finally the remodeling phase. The data indicate 1 mast cells appear in healing bone of WT mice but not Cpa3Cre/+ mice, beginning 14 days after surgery; 2 re-vascularization of repair tissue and deposition of mineralized bone was delayed and dis-organised in Cpa3Cre/+ mice compared with WT mice; 3 the defects in Cpa3Cre/+ mice were associated with little change in anabolic activity and biphasic alterations in osteoclast and macrophage activity. The outcome at 56 days postoperative was complete bridging of the defect in most WT mice and fibrous mal-union in most Cpa3Cre/+ mice. The results indicate that mast cells promote bone healing, possibly by recruiting vascular endothelial cells during the inflammatory phase and coordinating anabolic and catabolic activity during tissue remodeling. Taken together the data indicate that mast cells have a positive impact on bone repair.

  12. Clinical comparison between patients with selective immunoglobulin A deficiency and other primary immunodeficiencies.

    Science.gov (United States)

    Lozano, Natalia A; Lozano, Alejandro; Sasia, Laura V; Saranz, Ricardo J; Agresta, María Fernanda; del Pilar Bovina Martijena, María; Ianiero, Luciano; Grenat, Andrés R

    2015-04-01

    Primary immunodeficiencies (PID) are low-prevalence diseases. There are warning signs that may raise clinical suspicion. The objectives of this study were to describe the clinical characteristics and warning signs of patients with PID and to compare the clinical differences between selective immunoglobulin A (IgA) deficiency and other PIDs. Eighty-nine patients were studied; their median age at the time of diagnosis was 6 years old (4.08-11.67). Fifty-three (59.5%) patients were male. Fifty-four (60.7%) patients had selective IgA deficiency, and 35 (39.3%) had other PIDs. The main clinical manifestations were rhinopharyngitis in 65 (73.03%) patients and atopy in 39 (43.82%). Twenty- four (26.97%) patients showed warning signs, and none had selective IgA deficiency. Patients with other PIDs had a higher incidence of lower respiratory tract infection, sepsis, skin infections, mucocutaneous candidiasis, dental alterations, cardiovascular malformations, angioedema, hospitalizations and death. Ten (28.57%) patients received intravenous gammaglobulin, 15 (42.85%) antibiotic prophylaxis, and 2 (2.24%) antifungal prophylaxis.

  13. Attention impairments and ADHD symptoms in adult narcoleptic patients with and without hypocretin deficiency.

    Science.gov (United States)

    Filardi, Marco; Pizza, Fabio; Tonetti, Lorenzo; Antelmi, Elena; Natale, Vincenzo; Plazzi, Giuseppe

    2017-01-01

    Attentional complaints are common in narcolepsy patients and can overlap with daytime sleepiness features. Few studies attempted to characterize attentional domains in narcolepsy leading to controversial results. We aimed to assess the impact of hypocretin deficiency on attentional functioning by comparing performances on the attention network test (ANT) of narcoleptic patients with hypocretin deficiency (narcolepsy type 1-NT1) versus patients without hypocretin deficiency (narcolepsy type 2-NT2) and healthy controls. We also addressed frequency and severity of psychopathological symptoms and their influence on performances on ANT. Twenty-one NT1 patients, fifteen NT2 patients and twenty-two healthy controls underwent the ANT, which allows assessing three separate attentional processes (alerting, orienting and executive control), and a psychometric assessment including questionnaires on attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, anxiety and depression symptoms. NT1 and NT2 patients presented with slower reaction times compared to controls. NT1 patients exhibited an impairment of alerting network relative to NT2 and healthy controls, while orienting and executive control networks efficiency were comparable between groups. NT1 and NT2 displayed higher severity of ADHD inattentive domain than controls, NT1 patients also displayed higher severity of ADHD hyperactive domain and depressive symptoms. In NT1, ADHD and depressive symptoms were positively correlated. Despite a shared slowing of reaction times in both NT1 and NT2, a selective impairment of alerting network was present only in hypocretin deficient patients. Clinicians should carefully consider attentional deficits and psychopathological symptoms, including ADHD symptoms, in the clinical assessment and management of patients with narcolepsy.

  14. Attention impairments and ADHD symptoms in adult narcoleptic patients with and without hypocretin deficiency.

    Directory of Open Access Journals (Sweden)

    Marco Filardi

    Full Text Available Attentional complaints are common in narcolepsy patients and can overlap with daytime sleepiness features. Few studies attempted to characterize attentional domains in narcolepsy leading to controversial results. We aimed to assess the impact of hypocretin deficiency on attentional functioning by comparing performances on the attention network test (ANT of narcoleptic patients with hypocretin deficiency (narcolepsy type 1-NT1 versus patients without hypocretin deficiency (narcolepsy type 2-NT2 and healthy controls. We also addressed frequency and severity of psychopathological symptoms and their influence on performances on ANT.Twenty-one NT1 patients, fifteen NT2 patients and twenty-two healthy controls underwent the ANT, which allows assessing three separate attentional processes (alerting, orienting and executive control, and a psychometric assessment including questionnaires on attention-deficit hyperactivity disorder (ADHD, obsessive-compulsive disorder, anxiety and depression symptoms.NT1 and NT2 patients presented with slower reaction times compared to controls. NT1 patients exhibited an impairment of alerting network relative to NT2 and healthy controls, while orienting and executive control networks efficiency were comparable between groups. NT1 and NT2 displayed higher severity of ADHD inattentive domain than controls, NT1 patients also displayed higher severity of ADHD hyperactive domain and depressive symptoms. In NT1, ADHD and depressive symptoms were positively correlated.Despite a shared slowing of reaction times in both NT1 and NT2, a selective impairment of alerting network was present only in hypocretin deficient patients. Clinicians should carefully consider attentional deficits and psychopathological symptoms, including ADHD symptoms, in the clinical assessment and management of patients with narcolepsy.

  15. Deficient repair regulatory response to injury in keratoconic stromal cells.

    Science.gov (United States)

    Cheung, Isabella My; McGhee, Charles Nj; Sherwin, Trevor

    2014-05-01

    Keratoconus manifests as a conical protrusion of the cornea and is characterised by stromal thinning. This causes debilitating visual impairment, which may necessitate corneal transplantation. Hypothetically, many of the pathological features in keratoconus may be manifestations of defects in wound healing; however, as the pathobiology remains unclear, therapeutic targets related to disease mechanisms are currently lacking. This study investigated the protein expression of cytokines which may control stromal wound healing and the effect of an induced secondary injury (SI) on stromal cells from ex vivo human keratoconus and control corneas. Total protein was extracted from stromal cells from human keratoconic and non-keratoconic central corneas (n = 12) with (+SI) and without (-SI) an ex vivo corneal incision wound. The levels of interleukin 1 alpha (IL-1α), fibroblast growth factor 2 (FGF-2), nerve growth factor beta (β-NGF), insulin-like growth factor 1 (IGF-1), tumour necrosis factor alpha (TNF-α), epidermal growth factor (EGF), transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) were quantified using chemiluminescence-based immunoarrays. In stromal cells from -SI keratoconic corneas (compared with -SI normal corneas), the levels of IL-1α, IGF-1, TNF-α and TGF-β1 were increased and the levels of HGF and β-NGF were reduced. These alterations were also observed in +SI non-keratoconic corneas (compared with -SI non-keratoconic corneas). In stromal cells from +SI keratoconic corneas (compared with -SI keratoconic corneas), the quantities of IL-1α, FGF-2, TNF-a, EGF, TGF-a1 and PDGF were decreased. The repair-modulating milieu in keratoconic corneas appears comparable to that in wounded normal corneas. Moreover, wounded keratoconic corneas may be less capable of orchestrating a normal reparative response. These novel findings may improve our understanding of the pathobiology and may facilitate

  16. Orientação nutricional do paciente com deficiência de ferro Nutritional guidelines for patients with iron deficiency

    Directory of Open Access Journals (Sweden)

    Gisele A. Bortolini

    2010-06-01

    Full Text Available A deficiência de ferro ocorre quando as reservas nutricionais de ferro são esgotadas, principalmente devido ao balanço negativo entre ingestão e requerimentos de ferro. Quando a deficiência de ferro é severa desenvolve-se então a anemia por deficiência de ferro. A reposição dos estoques deve ser feita por meio de suplementação medicamentosa. A estratégia de educação nutricional, que visa o consumo quantitativo e qualitativo adequado de alimentos, fontes dos diversos nutrientes, é uma alternativa que possui baixo custo e não produz efeitos indesejáveis. O presente trabalho apresenta as recomendações nutricionais para a prevenção da deficiência de ferro e para o paciente com deficiência de ferro. A avaliação da ingestão alimentar e posterior orientação alimentar são importantes para contribuir com o tratamento e para mudar práticas alimentares, evitando assim a reocorrência da deficiência de ferro. Os grupos mais vulneráveis para a deficiência de ferro e que merecem atenção especial são as crianças, gestantes e mulheres em idade fértil.Iron deficiency occurs when nutritional iron reserves are used up mainly as a result of a negative balance between intake and requirements. When iron deficiency is severe, the patient evolves with iron deficiency anaemia. Replacement of iron reserves is normally by means of a medicinal supplement. One low cost alternative that does not present unwanted side effects is nutritional education which aims at quantitatively and qualitatively improving the consumption of foods and thus provide a healthy diet. The current study presents nutritional guidelines both for the prevention and treatment of iron deficiency anaemia. It is important that an evaluation of dietary intake is made and that dietary counseling is followed to assist treatment and to change eating habits, thereby preventing the recurrence of iron deficiency. The most vulnerable groups for iron deficiency warrant

  17. Triacylglycerol infusion improves exercise endurance in patients with mitochondrial myopathy due to complex I deficiency

    NARCIS (Netherlands)

    Roef, MJ; de Meer, K; Reijngoud, DJ; Straver, HWHC; de Barse, M; Kalhan, SC; Berger, R

    Background: A high-fat diet has been recommended for the treatment of patients with mitochondrial myopathy due to complex I (NADH dehydrogenase) deficiency (CID). Objective: This study evaluated the effects of intravenous infusion of isoenergetic amounts of triacylglycerol or glucose on substrate

  18. Perioperative challenges in a patient of severe G6PD deficiency undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Vivek Chowdhry

    2012-01-01

    Full Text Available We describe a successful perioperative management of a case of 38-year-old male, presented with chronic jaundice with severe mitral stenosis and moderate tricuspid regurgitation; upon evaluation, he was found to have severe glucose-6-phosphate dehydrogenase (G6PD deficiency. Usually, patients deficient in G6PD exhibit increased hemolysis andtherefore increased need for blood transfusion after cardiac surgery as well as impaired oxygenation in the postoperative period leading to prolonged ventilation. On reperfusion after a period of ischemia, the antioxidant system recruits all of its components in an attempt to neutralize the overwhelming oxidative stress of free radicals, as the free radical scavenging system is deficient in these patients, the chances of free-radical-induced injury is more. Our patient underwent mitral valve replacement and tricuspid annuloplasty under cardiopulmonary bypass with necessary precautions to reduce the formation of free radicals. Treatment was targeted toward theprevention of free radical injuryin the G6PD-deficient patient. He had an uneventful intraoperative and postoperative course.

  19. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

  20. Mismatch repair deficiency in colorectal cancer patients in a low ...

    African Journals Online (AJOL)

    Background. In a previous study we identified 206 patients with colorectal adenocarcinoma in the Northern Cape province of South Africa, diagnosed between January 2002 and February 2009. The age-standardised incidence was 4.2/100 000 per year world standard population. This is 10% of the rate reported in ...

  1. Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh

    Directory of Open Access Journals (Sweden)

    Alabdulaali Mohammed

    2010-01-01

    Full Text Available Background and Aims: Blood donation from glucose-6-phosphate dehydrogenase (G6PD-deficient and sickle cell trait (SCT donors might alter the quality of the donated blood during processing, storage or in the recipient′s circulatory system. The aim of this study was to determine the prevalence of G6PD deficiency and SCT among blood donors coming to King Khalid University Hospital (KKUH in Riyadh. It was also reviewed the benefits and risks of transfusing blood from these blood donors. Materials and Methods: This cross-sectional study was conducted on 1150 blood samples obtained from blood donors that presented to KKUH blood bank during the period April 2006 to May 2006. All samples were tested for Hb-S by solubility test, alkaline gel electrophoresis; and for G6PD deficiency, by fluorescent spot test. Results: Out of the 1150 donors, 23 (2% were diagnosed for SCT, 9 (0.78% for G6PD deficiency and 4 (0.35% for both conditions. Our prevalence of SCT and G6PD deficiency is higher than that of the general population of Riyadh. Conclusion: We recommend to screen all units for G6PD deficiency and sickle cell trait and to defer donations from donors with either of these conditions, unless if needed for special blood group compatibility, platelet apheresis or if these are likely to affect the blood bank inventory. If such blood is to be used, special precautions need to be undertaken to avoid complications in high-risk recipients.

  2. [Thunder-fire Moxibustion forQiDeficiency-induced Fatigue in Breast Cancer Patients Under-going Chemotherapy].

    Science.gov (United States)

    Lu, Lu; Li, Wei-Han; Guo, Xiao-Chuan; Fu, Wen-Bin

    2018-02-25

    To observe the clinical effect of thunder-fire moxibustion in the treatment of qi deficiency-induced fatigue in breast cancer patients undergoing chemotherapy. Sixty breast cancer patients undergoing chemotherapy were randomly divided into thunder-fire moxibustion (Moxi) and conventional nursing (nursing) groups ( n =30 in each group). Patients in the Moxi group were treated with thunder-fire moxibustion applied to the back part of body from Pishu (BL 20) to Qihaishu (BL 24) on the bilateral sides and to the abdominal part from Zhongwan (CV 12) to Guanyuan (CV 4) for 30 min, once a day for 14 days. Patients in the nursing group were treated with health education and conventional nursing care. The simple fatigue scale, traditional Chinese medicine (TCM) syndrome score, clinical curative effect were observed before and after the treatment, and white blood cell (WBC) count was observed 5 days ofter chemotherapy and after the treatment respectively. After the treatment, the simple fatigue scales and TCM syndrome scores were significantly decreased and WBC counts were significantly increased in both groups relevant to their individual pre-treatment ( P Thunder-fire moxibustion can effectively relieve the degree of fatigue and the symptoms of qi deficiency in breast cancer patients undergoing chemotherapy.

  3. Nocturnal Rapid Eye Movement Sleep Latency for Identifying Patients With Narcolepsy/Hypocretin Deficiency

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E.; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O’Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2014-01-01

    IMPORTANCE Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. OBJECTIVE To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. DESIGN, SETTING, AND PARTICIPANTS Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. MAIN OUTCOME AND MEASURES Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal

  4. Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.

    Science.gov (United States)

    Andlauer, Olivier; Moore, Hyatt; Jouhier, Laura; Drake, Christopher; Peppard, Paul E; Han, Fang; Hong, Seung-Chul; Poli, Francesca; Plazzi, Giuseppe; O'Hara, Ruth; Haffen, Emmanuel; Roth, Thomas; Young, Terry; Mignot, Emmanuel

    2013-07-01

    Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically. To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency. Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels. Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg

  5. High prevalence of vitamin D deficiency and its association with metabolic disorders in elderly patients

    Directory of Open Access Journals (Sweden)

    Małgorzata Koziarska-Rościszewska

    2017-12-01

    Full Text Available Background . Vitamin D is considered to be an important co-factor of metabolic processes. However, the available data is ambiguous. Some data indicates an important role of vitamin D in adipocyte metabolism, and hence also in obesity – a well-known risk factor of diabetes mellitus and cardiovascular diseases (CVD. Objectives . To assess the prevalence of vitamin D deficiency and to evaluate the relationship between serum 25(OHD concentration and metabolic disorders in elderly patients attending primary care. Material and methods . This observational study was performed on 110 elderly patients: 88 females, 22 males, Caucasian, > 60 years. A questionnaire was completed concerning lifestyle and chronic diseases. Clinical examination, anthropometric measurements and laboratory tests (25(OHD, lipids, glycemia, blood morphology, serum creatinine, PT H were performed. BMI and WHR were calculated. Patients reporting physical activity (walking, Nordic walking, swimming, cycling, other ≥ 150 minutes per week were classified as “physically active”. Results . Vitamin D deficiency (25(OHD < 30 ng/ml; < 75 nmol/l was found in 84.5%, extreme deficiency (< 10 ng/ml; < 25 nmol/l in 6.3%. A significant correlation between serum vitamin D deficiency and visceral obesity was found (p = 0.02. No correlation was found with BMI, physical activity, lipids, diabetes or CVD. Conclusions . Vitamin D deficiency was found to be highly prevalent in the examined group of elderly people. Visceral obesity in the elderly is associated with vitamin D deficiency. Vitamin D supplementation may supposedly contribute to prevention of obesity and its treatment.

  6. Red cell indices and discriminant functions in the detection of beta-thalassaemia trait in a population with high prevalence of iron deficiency anaemia.

    Science.gov (United States)

    Madan, N; Sikka, M; Sharma, S; Rusia, U; Kela, K

    1999-01-01

    Red cell indices and discriminant functions were studied in 463 heterozygous beta-thalassaemics (337 without iron deficiency, 126 with iron deficiency) and 195 patients of iron deficiency anaemia (IDA) to ascertain their utility in the detection of betathalassaemia trait (BTT). Majority of traits in both groups had an elevated RBC count (> or = 5.0 x 10(12)/L). The counts were significantly higher than of patients with IDA, only 4.6% of whom had this degree of erythrocytosis. Mean Hb concentration was significantly higher in traits as compared to iron deficient subjects (p < 0.0001). Mean MCV and MCH were significantly (p < 0.0001) lower in traits more so in those with ID as compared to patients of IDA. MCV < 80 fl and MCH < 27 pg were found to be sensitive markers in the detection of traits even in the presence of ID. Of the four discriminant functions studied MCSQ was found to be most sensitive in detection of BTT and it identified 97.9% traits. DF of England and Fraser was most specific for BTT being < 8.4 in only 6.2% patients with IDA. Detection of erythrocytosis especially in the presence of mild anaemia and calculation of discriminant functions derived from red cell indices were found to play an important role in screening for BTT even in the presence of ID and helped identify those patients who required further laboratory evaluation.

  7. Irreversible AE1 tyrosine phosphorylation leads to membrane vesiculation in G6PD deficient red cells.

    Directory of Open Access Journals (Sweden)

    Antonella Pantaleo

    Full Text Available BACKGROUND: While G6PD deficiency is one of the major causes of acute hemolytic anemia, the membrane changes leading to red cell lysis have not been extensively studied. New findings concerning the mechanisms of G6PD deficient red cell destruction may facilitate our understanding of the large individual variations in susceptibility to pro-oxidant compounds and aid the prediction of the hemolytic activity of new drugs. METHODOLOGY/PRINCIPAL FINDINGS: Our results show that treatment of G6PD deficient red cells with diamide (0.25 mM or divicine (0.5 mM causes: (1 an increase in the oxidation and tyrosine phosphorylation of AE1; (2 progressive recruitment of phosphorylated AE1 in large membrane complexes which also contain hemichromes; (3 parallel red cell lysis and a massive release of vesicles containing hemichromes. We have observed that inhibition of AE1 phosphorylation by Syk kinase inhibitors prevented its clustering and the membrane vesiculation while increases in AE1 phosphorylation by tyrosine phosphatase inhibitors increased both red cell lysis and vesiculation rates. In control RBCs we observed only transient AE1 phosphorylation. CONCLUSIONS/SIGNIFICANCE: Collectively, our findings indicate that persistent tyrosine phosphorylation produces extensive membrane destabilization leading to the loss of vesicles which contain hemichromes. The proposed mechanism of hemolysis may be applied to other hemolytic diseases characterized by the accumulation of hemoglobin denaturation products.

  8. Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice.

    Science.gov (United States)

    Zheng, Lingjie; Sharma, Rahul; Kung, John T; Deshmukh, Umesh S; Jarjour, Wael N; Fu, Shu Man; Ju, Shyr-Te

    2008-04-01

    We hypothesize that regulatory T-cell (Treg)-deficient strains have an altered TCR repertoire in part due to the expansion of autoimmune repertoire by self-antigen. We compared the Vbeta family expression profile between B6 and Treg-lacking B6.Cg-Foxp3(sf)(/Y) (B6.sf) mice using fluorescent anti-Vbeta mAbs and observed no changes. However, while the spectratypes of 20 Vbeta families among B6 mice were highly similar, the Vbeta family spectratypes of B6.sf mice were remarkably different from B6 mice and from each other. Significant spectratype changes in many Vbeta families were also observed in Treg-deficient IL-2 knockout (KO) and IL-2Ralpha KO mice. Such changes were not observed with anti-CD3 mAb-treated B6 mice or B6 CD4+CD25- T cells. TCR transgenic (OT-II.sf) mice displayed dramatic reduction of clonotypic TCR with concomitant increase in T cells bearing non-transgenic Vbeta and Valpha families, including T cells with dual receptors expressing reduced levels of transgenic Valpha and endogenous Valpha. Collectively, the data demonstrate that Treg deficiency allows polyclonal expansion of T cells in a stochastic manner, resulting in widespread changes in the TCR repertoire.

  9. Primary cardiac lymphoma in a patient with acquired immune deficiency syndrome

    International Nuclear Information System (INIS)

    Constantino, A.; West, T.E.; Gupta, M.; Loghmanee, F.

    1987-01-01

    A 34-year-old male prisoner with a history of intravenous drug abuse presented with fever, lymphadenopathy, weight loss, and recent onset of congestive heart failure. Serologic testing was positive for antibodies to human immune deficiency virus. There was intense myocardial uptake of gallium. Autopsy showed a primary immunoblastic lymphoma involving only the myocardium. While primary cardiac lymphoma is an extremely rare condition, the incidence may be higher in patients with acquired immune deficiency syndrome (AIDS) and should be suspected in cases with atypical cardiomyopathy

  10. Growth Hormone Deficiency in a Patient with Becker Muscular Dystrophy: A Pediatric Case Report

    Directory of Open Access Journals (Sweden)

    Valeria Calcaterra

    2013-01-01

    Full Text Available Objective. To describe a biochemical growth hormone (GH deficiency and to evaluate therapeutic result in a six-year-old male with Becker muscular dystrophy (BMD. Methods. GH peak was evaluated after response to arginine and insulin. Bone age was evaluated according to Greulich and Pyle method. Results. The GH-supplementary therapy was very effective in terms of growth gain. Conclusion. The possibility of a growth hormone deficiency and treatment with GH in patients with BMD cannot be excluded, especially considering the good therapeutic response.

  11. A Metabolomics Approach to Stratify Patients Diagnosed with Diabetes Mellitus into Excess or Deficiency Syndromes

    Directory of Open Access Journals (Sweden)

    Tao Wu

    2015-01-01

    Full Text Available The prevalence of type 2 diabetes continuously increases globally. The traditional Chinese medicine (TCM can stratify the diabetic patients based on their different TCM syndromes and, thus, allow a personalized treatment. Metabolomics is able to provide metabolite biomarkers for disease subtypes. In this study, we applied a metabolomics approach using an ultraperformance liquid chromatography (UPLC coupled with quadruple-time-of-flight (QTOF mass spectrometry system to characterize the metabolic alterations of different TCM syndromes including excess and deficiency in patients diagnosed with diabetes mellitus (DM. We obtained a snapshot of the distinct metabolic changes of DM patients with different TCM syndromes. DM patients with excess syndrome have higher serum 2-indolecarboxylic acid, hypotaurine, pipecolic acid, and progesterone in comparison to those patients with deficiency syndrome. The excess patients have more oxidative stress as demonstrated by unique metabolite signatures than the deficiency subjects. The results provide an improved understanding of the systemic alteration of metabolites in different syndromes of DM. The identified serum metabolites may be of clinical relevance for subtyping of diabetic patients, leading to a personalized DM treatment.

  12. Association between vitamin D deficiency and anemia in inflammatory bowel disease patients with ileostomy

    Directory of Open Access Journals (Sweden)

    Andre Fialho

    2015-07-01

    Full Text Available Background: Vitamin D deficiency is commonly seen in patients with inflammatory bowel disease (IBD. Vitamin D deficiency in IBD patients with ileostomy has not been systemically studied. The aim of the study was to assess the frequency and risk factors associated with low 25(OH D3 levels in those patients. Methods: 112 eligible IBD patients with ileostomy were studied. Demographic, clinical, and endoscopic variables were analyzed. Vitamin D levels before and after ileostomy were compared when available. Levels of serum 25(OHD3 <20 ng/mL were classed as being deficient. Results: 112 eligible ileostomy patients were included. The mean vitamin D level was 21.47 ± 1.08 ng/dl. Low levels of vitamin D (<30 ng/dl were present in 92 patients (82%. Vitamin D deficiency (<20 ng/dL was seen in 55 patients (49%. There was no difference between patients with or without vitamin D deficiency regarding demographic variables, medication use and duration of ileostomy. Neo-ileal inflammation on endoscopy was not associated with vitamin D deficiency (p = 0.155. Lower levels of phosphorus (p = 0.020 or hemoglobin (p = 0.019 and shorter duration of IBD (p = 0.047 were found in patients with vitamin D deficiency. In multivariate analysis, lower levels of phosphorus (odds ratio [OR]: 1.83, 95% confidence interval [CI]: 1.16–2.89, p = 0.009 and hemoglobin (OR: 1.32, 95% CI: 1.08–1.60, p = 0.006 remained significantly associated with vitamin D deficiency. Conclusion: Vitamin D deficiency is common in IBD patients with ileostomy and is associated with low hemoglobin levels. Further studies are needed to evaluate vitamin D supplementation as a possible adjuvant in the treatment of anemia of chronic disease in IBD patients. Resumo: Introdução: A deficiência de vitamina D em pacientes com doença inflamatória intestinal submetidos a ileostomia não foi estudada sistematicamente. O objetivo desse estudo foi avaliar a frequência e os fatores de

  13. Vitamin D Deficiency and Associated Factors in Patients with Mental Disorders Treated in Routine Practice.

    Science.gov (United States)

    Ristic, Svetlana; Zivanovic, Sandra; Milovanovic, Dragan R; Janjic, Vladimir; Djokovic, Danijela; Jovicevic, Ana; Pirkovic, Marijana Stanojevic; Kocic, Sanja

    2017-01-01

    This research aimed to investigate factors associated with vitamin D deficiency and to provide data about its prevalence in patients suffering from different psychiatric illnesses. The study had a cross-sectional design and it included 220 patients of both genders, aged from 19-81 y, with a wide range of mental disorders (F00-F89), and treated in routine ambulatory and hospital practice. The researchers collected data from three sources: medical records, a study questionnaire and biochemical analysis of patients' serum samples (concentration of vitamin D measured as 25(OH)D, calcium, phosphorus, magnesium, sodium and potassium). Data were analyzed using descriptive statistics, methods for hypothesis testing and binary logistic regression, at the p≤0.05 level. A total of 140 patients (64%) had a deficiency of vitamin D (20 ng/mL). Among variables related to demographics, life style habits, mental illness, comorbid disorders and drugs, two of them, female gender (odds ratio (OR)=2.5, 95% confidence interval (CI)=1.3-4.9, p=0.006) and using clozapine (OR=15.6, 95% CI 1.7-144.7, p=0.02), were significantly associated with vitamin D deficiency. Physical activity (OR= 0.4, 95% CI 0.2-0.9, p=0.02), exercising (OR=0.2, 95% CI deficiency cut-off level. Patients with mental disorders are at high risk for vitamin D deficiency, particularly females and clozapine users as well as those having no adequate physical activity or dietary habits.

  14. Novel CFI mutation in a patient with leukocytoclastic vasculitis may redefine the clinical spectrum of Complement Factor I deficiency

    DEFF Research Database (Denmark)

    Bay, Jakob Thaning; Katzenstein, Terese Lea; Kofoed, Kristian

    2015-01-01

    presentation of Factor I deficiency varies and includes severe recurrent bacterial infections, glomerulonephritis and autoimmune diseases. The patient, a 28-years old woman with consanguineous parents, presented with recurrent leukocytoclastic vasculitis in the lower extremities with no associated systemic...... mutations vary among patients sole association with leukocytoclastic vasculitis redefines the clinical spectrum of complete Factor I deficiency....

  15. Gene Expression Profiles of HIV/AIDS Patients with Qi-Yin Deficiency and Dampness-Heat Retention.

    Science.gov (United States)

    Liu, Sa; Chen, Yulong; Xie, Shiping; Xu, Qianlei; Chen, Jianshe; Wang, Changhai; Wang, Zhao; Ma, Suna; Wu, Xingwei; Zhang, Ning

    2016-11-01

    Traditional Chinese Medicine (TCM) applied in the clinic as a complementary and alternative therapy has helped improve immunity and reduce side effects and symptomatic treatment in patients with HIV/AIDS. However, the mechanisms of TCM syndromes are not clear. Transcriptomics enables the study of such TCM syndromes. This study compared the messenger RNA (mRNA) expressions of healthy persons and patients with HIV/AIDS who had two common TCM syndromes, qi-yin deficiency and dampness-heat retention, to find the difference in HIV/AIDS with TCM syndromes. Comparison with healthy persons identified 113 mRNAs-41 enhanced and 72 decreased-in the qi-yin deficiency group. Additionally, 76 mRNAs were found in the dampness-heat retention group: 14 increased and 62 decreased. Functional genetic analysis of the mRNAs indicated that two TCM syndromes were correlated with cell apoptosis, immunoinflammatory responses, and lymphocyte activation. Differentially expressed mRNAs in the qi-yin deficiency group were obviously associated with cellular activity, communication, protein localization, cellular ion homeostasis, and regulation of cell motion, whereas mRNAs in the dampness-heat retention group were associated with sequence-specific DNA binding, cellular response to stress, and hemopoietic or lymphoid organ development. These results suggest that the formation of different TCM syndromes in patients with HIV/AIDS were founded on biological transcriptomics, which reveal mechanisms of the formation of these syndromes in HIV/AIDS. Differentially expressed mRNAs in two TCM syndrome groups tended to normalize after TCM intervention, which indicates that TCM might remit symptoms by changing genetic expression.

  16. Nitric oxide acts upstream of ethylene in cell wall phosphorus reutilization in phosphorus-deficient rice.

    Science.gov (United States)

    Zhu, Xiao Fang; Zhu, Chun Quan; Wang, Chao; Dong, Xiao Ying; Shen, Ren Fang

    2017-01-01

    Nitric oxide (NO) and ethylene are both involved in cell wall phosphorus (P) reutilization in P-deficient rice; however, the crosstalk between them remains unclear. In the present study using P-deficient 'Nipponbare' (Nip), root NO accumulation significantly increased after 1 h and reached a maximum at 3 h, while ethylene production significantly increased after 3 h and reached a maximum at 6 h, indicating NO responded more quickly than ethylene. Irrespective of P status, addition of the NO donor sodium nitroprusside (SNP) significantly increased while the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO) significantly decreased the production of ethylene, while neither the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) nor the ethylene inhibitor aminoethoxyvinylglycine (AVG) had any influence on NO accumulation, suggesting NO acted upstream of ethylene. Under P-deficient conditions, SNP and ACC alone significantly increased root soluble P content through increasing pectin content, and c-PTIO addition to the ACC treatment still showed the same tendency; however, AVG+SNP treatment had no effect, further indicating that ethylene was the downstream signal affecting pectin content. The expression of the phosphate transporter gene OsPT2 showed the same tendency as the NO-ethylene-pectin pathway. Taken together, we conclude that ethylene functions downstream of NO in cell wall P reutilization in P-deficient rice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  17. The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Schmid ST

    2012-09-01

    Full Text Available ST Schmid,1 J Koepke,1 M Dresel,1 A Hattesohl,1 E Frenzel,2 J Perez,3 DA Lomas,4 E Miranda,5 T Greulich,1 S Noeske,1 M Wencker,6 H Teschler,6 C Vogelmeier,1 S Janciauskiene,2,* AR Koczulla1,*1Department of Internal Medicine, Division for Pulmonary Diseases, University Hospital Marburg, Marburg, Germany; 2Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 3Department of Cellular Biology, University of Malaga, Malaga, Spain; 4Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 5Department of Biology and Biotechnology, Istituto Pasteur – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy; 6Department of Pneumology, West German Lung Clinic, Essen University Hospital, Essen, Germany*These authors contributed equally to this workBackground: The major concept behind augmentation therapy with human α1-antitrypsin (AAT is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema.Objective: To evaluate the short-term effects of augmentation therapy (Prolastin® on plasma levels of AAT, C-reactive protein, and chemokines/cytokines.Materials and methods: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12 on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL.Results: There were significant fluctuations in serum (but not in exhaled breath condensate levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL

  18. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency.

    Science.gov (United States)

    Tachdjian, Raffi

    2013-12-01

    Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.

  19. Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

    DEFF Research Database (Denmark)

    Hitz, Mette Friberg; Jensen, Jens-Erik Beck; Eskildsen, Peter C

    2006-01-01

    OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium...... identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH...... to healthy control subjects GH-deficient males had, in contrast to GH-deficient females, significantly reduced BMD and BMC. This obvious gender difference seems to be caused by the oestrogen substitution given to the females, compensating for the lack of GH, an effect testosterone does not seem to possess...

  20. Work-family conflict, psychological distress, and sleep deficiency among patient care workers.

    Science.gov (United States)

    Jacobsen, Henrik B; Reme, Silje Endresen; Sembajwe, Grace; Hopcia, Karen; Stoddard, Anne M; Kenwood, Christopher; Stiles, Tore C; Sorensen, Glorian; Buxton, Orfeu M

    2014-07-01

    This study examined whether work-family conflict was associated with sleep deficiencies, both cross-sectionally and longitudinally. In this two-phase study, a workplace health survey was completed by a cohort of patient care workers (n = 1,572). Additional data were collected 2 years later from a subsample of the original respondents (n = 102). Self-reported measures included work-family conflict, workplace factors, and sleep outcomes. The participants were 90% women, with a mean age of 41 ± 11.7 years. At baseline, after adjusting for covariates, higher levels of work-family conflict were significantly associated with sleep deficiency. Higher levels of work-family conflict also predicted sleep insufficiency nearly 2 years later. The first study to determine the predictive association between work-family conflict and sleep deficiency suggests that future sleep interventions should include a specific focus on work-family conflict. Copyright 2014, SLACK Incorporated.

  1. Association of dyslipidaemia in patients with varying degrees of Vitamin D deficiency in the Asian population.

    Science.gov (United States)

    Arif, Mohammad Ali; Niazi, Rauf; Arif, Saba Ali

    2017-12-01

    To investigate the associations of dyslipidaemia with varying levels of 25 hydroxy vitamin D3 deficiency. This cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July 2016 to January 2017, and comprised patients having varying levels of 25 hydroxy vitamin D3 deficiency. Patients were stratified according to the severity of deficiency and had their serum fasting lipid profiles measured. SPSS 20 was used for data analysis. Of the 175 participants, 124(70.9%) were female and 51(29.1%) were male. The overall mean age of the patients was 47.7±12.2 years (range: 18-65 years). A very strong inverse correlation was found between vitamin D levels and low-density lipoprotein cholesterol (p<0.001) and a similar trend was obtained for vitamin D and total cholesterol (p<0.001). With regards to triglycerides, a modest inverse correlation was found (p=0.05). No significant association was documented between 25 hydroxy vitamin D3 levels and high-density lipoprotein cholesterol (p=0.3). An inversely proportional relationship was found between total cholesterol, low-density lipoprotein cholesterol and triglycerides against varying levels of vitamin D deficiency.

  2. Differences of Excess and Deficiency Zheng in Patients with Chronic Hepatitis B by Urinary Metabonomics

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    Shujun Sun

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM physicians stratify patients with the same disease into different subtypes in order to guide the appropriate treatment, which is called Zheng (TCM syndrome classification. Excess and deficiency ZHENG is a couple of basic ZHENGs of maladjusted body nature, reflecting the struggling state of human body and pathogenic factor and is important and prevalently exists in the ZHENG classification of many diseases. The present work using chronic hepatitis B (CHB as an entry point explored the substance connotation of excess and deficiency ZHENG with the metabonomic technology based on gas chromatography-mass spectrometry (GC-MS. The different substantial basis of two ZHENGs suggested that CHB patients could be categorized into two groups with diverse pathogenesis. The differential metabolites and disturbed pathways compared to not-obvious ZHENG characters patients (without ZHENG group/WZ were selected in both of the two ZHENGs. The ROC analysis demonstrated that five metabolites had a greater potential to be the clinic biomarkers of EZ or DZ. And excess ZHENG revealed a higher level of immune function than deficiency ZHENG. We are eager to transform the concept of traditional excess and deficiency ZHENGs to modern therapeutic approaches, with the prospect to help to promote personalized medicine.

  3. Possible fenugreek induced haemolysis in a patient with previously unknown G6PD deficiency.

    Science.gov (United States)

    Sadler, Joseph Marshall; Ash, Stephen; Brito-Babapulle, Finella Marie

    2009-01-01

    Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most common disease producing enzymopathy. People with G6PD deficiency cannot cope with oxidative stressors. These patients are asymptomatic until they develop a haemolytic crisis which presents as anaemia and jaundice. The agents known to cause haemolysis in these patients are: oxidant drugs, (primaquine, chloroquine and other anti-malarials), antibiotics, (chloramphenicol, nitrofurantoin, sulphonamides, and all quinolone antibiotics). Chemicals to be avoided are moth balls (napththalene), aniline dyes, and some Chinese herbal medicine (San Chi, Chuan Lian). The classic presentation of exposure to Fava beans (legumes), causing oxidative haemolysis, has led G6PD deficiency to be also known as Favism. The patient we present here had no exposure to any of the known causes of oxidative haemolysis. Instead his precipitating cause strongly suggests raw fenugreek (T foenum-graecum L), a legume used as a herbal treatment for diabetes and previously not known to be a precipitant of haemolysis in G6PD deficiency.

  4. Position paper on management of iron deficiency in adult cancer patients.

    Science.gov (United States)

    Barni, Sandro; Gascòn, Pere; Petrelli, Fausto; García-Erce, José Antonio; Pedrazzoli, Paolo; Rosti, Giovanni; Giordano, Giulio; Mafodda, Antonio; Múñoz, Manuel

    2017-08-01

    Disorders of iron metabolism are commonly seen in onco-hematological clinical practice. Iron-deficiency anemia and cancer-associated anemia are usually treated with supportive therapies. Optimal management of these conditions are discussed in this perspective paper. Areas covered: A position paper discussing a number of hot topics on anemia in cancer patients is presented. The main areas covered by experts in the field are: definitions, prevalence and consequences of anemia and iron deficiency, incidence of anemia resulting from targeted therapies, importance of anemia diagnosis and monitoring, evaluation of iron status before and during treatment, role of transfusions and erythropoiesis-stimulating agents, management of iron deficiency with or without anemia, parenteral iron supplementation, role of new oral iron formulations, safety and cost issues regarding different iron compounds and administration routes. Expert commentary: Despite the availability of newer therapeutic options for its management, anemia still represents a major complication of treatment in cancer patients (surgery, chemotherapy, radiotherapy, targeted therapies), aggravating physical impairment, and negatively affecting general outcome. The view expressed by the panelists, attendees of the 4th Mediterranean Course on Iron Anemia, summarizes what they consider optimal clinical practice for screening, diagnosis, treatment and monitoring of iron deficiency and anemia in cancer patients.

  5. Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency

    Directory of Open Access Journals (Sweden)

    Niu Li

    2017-04-01

    Full Text Available Fructose-1,6-bisphosphatase (FBPase deficiency is a rare, autosomal recessive inherited disease caused by the mutation of the FBP1 gene, the incidence is estimated to be between 1/350,000 and 1/900,000. The symptoms of affected individuals are non-specific and are easily confused with other metabolic disorders. The present study describes the clinical features of four Chinese pediatric patients who presented with hypoglycemia, hyperlactacidemia, metabolic acidosis, and hyperuricemia. Targeted-next generation sequencing using the Agilent SureSelect XT Inherited Disease Panel was used to screen for causal variants in the genome, and the clinically-relevant variants were subsequently verified using Sanger sequencing. Here, DNA sequencing identified six variations of the FBP1 gene (NM_000507.3 in the four patients. In Case 1, we found a compound heterozygous mutations of c.704delC (p.Pro235GlnfsX42 (novel and c.960_961insG (p.Ser321Valfs (known pathogenic. In Case 2, we found a compound heterozygous mutations of c.825 + 1G>A and c.960_961insG (both were known pathogenically. In Case 3, a homozygous missense mutation of c.355G>A (p.Asp119Asn (reported in ClinVar database without functional study was found. Case 4 had a compound heterozygous mutations c.720_729del (p.Tyr241GlyfsX33 (novel and c.490G>A (p.Gly164Ser (known pathogenically. Further in vitro studies in the COS-7cell line demonstrated that the mutation of ASP119ASN had no impact on protein expression, but decreased the enzyme activity, and with which the clinical significance of Asp119Asn can be determined to be likely pathogenic. This report not only expands upon the known spectrum of variation of the FBP1 gene, but also deepens our understanding of the clinical features of FBPase deficiency.

  6. Reconstruction of limbal stem cell deficient corneal surface with induced human bone marrow mesenchymal stem cells on amniotic membrane.

    Science.gov (United States)

    Rohaina, Che Man; Then, Kong Yong; Ng, Angela Min Hwei; Wan Abdul Halim, Wan Haslina; Zahidin, Aida Zairani Mohd; Saim, Aminuddin; Idrus, Ruszymah B H

    2014-03-01

    The cornea can be damaged by a variety of clinical disorders or chemical, mechanical, and thermal injuries. The objectives of this study were to induce bone marrow mesenchymal stem cells (BMSCs) to corneal lineage, to form a tissue engineered corneal substitute (TEC) using BMSCs, and to treat corneal surface defects in a limbal stem cell deficiency model. BMSCs were induced to corneal lineage using limbal medium for 10 days. Induced BMSCs demonstrated upregulation of corneal stem cell markers; β1-integrin, C/EBPδ, ABCG2, and p63, increased protein expression of CK3 and p63 significantly compared with the uninduced ones. For TEC formation, passage 1 BMSCs were trypsinized and seeded on amniotic membrane in a transwell co-culture system and were grown in limbal medium. Limbal stem cell deficiency models were induced by alkaline injury, and the TEC was implanted for 8 weeks. Serial slit lamp evaluation revealed remarkable improvement in corneal regeneration in terms of corneal clarity and reduced vascularization. Histologic and optical coherence tomography analyses demonstrated comparable corneal thickness and achieved stratified epithelium with a compact stromal layer resembling that of normal cornea. CK3 and p63 were expressed in the newly regenerated cornea. In conclusion, BMSCs can be induced into corneal epithelial lineage, and these cells are viable for the formation of TEC, to be used for the reconstruction of the corneal surface in the limbal stem cell deficient model. Copyright © 2014 Mosby, Inc. All rights reserved.

  7. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency

    DEFF Research Database (Denmark)

    Abolhassani, Hassan; Edwards, Emily S. J.; Ikinciogullari, Aydan

    2017-01-01

    is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70-CD27 interactions therefore play a nonredundant role in T and B cell-mediated immunity, especially for protection against EBV and humoral immunity.......In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma...... and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal...

  8. Preferential radiosensitization of G1 checkpoint--deficient cells by methylxanthines

    International Nuclear Information System (INIS)

    Russell, Kenneth J.; Wiens, Linda W.; Demers, G. William; Galloway, Denise A.; Le, Tiep; Rice, Glenn C.; Bianco, James A.; Singer, Jack W.; Groudine, Mark

    1996-01-01

    Purpose: To develop a checkpoint-based strategy for preferential radiosensitization of human tumors with deficient and/or mutant p53. Methods and Materials: A549 human lung adenocarcinoma cell lines differing in their expression of the p53 tumor suppressor gene were produced by transduction with the E6 oncogene from human papilloma virus type 16. The cells expressing E6 (E6+) lack a G1 arrest in response to ionizing radiation, are deficient in p53 and p21 expression, and exhibit a fivefold greater clonogenic survival following 10 Gy radiation. Results: Postirradiation incubation with millimolar concentrations of the methylxanthine pentoxifylline (PTX) results in preferential radiosensitization of the E6+ cells compared to the LXSN+ vector transduced controls. There is a threefold sensitization of the LXSN+ cells and a 15-fold sensitization of the E6+ cells, which results in equal clonogenic survival of the two lines. Flow cytometry reveals PTX abrogation of the radiation induced G2 arrest for both cell lines. PTX also prolongs G1 transit for both cell lines. Preliminary results are presented using a novel methylxanthine, lisofylline (LSF), which has similar cell cycle effects on G1 and G2 and achieves differential radiosensitization at micromolar concentrations that are sustainable in humans. Conclusions: This checkpoint-based strategy is a promising approach for achieving preferential radiosensitization of p53- tumors relative to p53+ normal tissues

  9. Clinical, biochemical and molecular findings in seven Polish patients with adenylosuccinate lyase deficiency.

    Science.gov (United States)

    Jurecka, Agnieszka; Zikanova, Marie; Tylki-Szymanska, Anna; Krijt, Jakub; Bogdanska, Anna; Gradowska, Wanda; Mullerova, Karolina; Sykut-Cegielska, Jolanta; Kmoch, Stanislav; Pronicka, Ewa

    2008-08-01

    Adenylosuccinate lyase (ADSL) catalyzes two steps in purine nucleotide metabolism-the 8th step in the de novo pathway: conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR), and conversion of adenylosuccinate (S-AMP) to adenylate (AMP) in the purine nucleotide cycle. To date, over 50 patients have been reported suffering from ADSL deficiency. We report all seven so far diagnosed Polish patients with this defect. Most of our patients shared intractable seizures and psychomotor retardation since the neonatal period and had biochemical evidence of severe (type I) deficiency. Two patients with type II suffered only from mild/moderate psychomotor retardation and showed a transientvisual contact disturbance. One patient had a fatal neonatal form of ADSL deficiency with lack of spontaneous movement, respiratory failure, severe encephalopathy and intractable seizures. Analysis of the ADSL gene showed that four apparently unrelated patients carried a R426H mutation (two homozygous and two compound heterozygous). With the exception of the latter mutation, a Y114H mutation that had been reported previously, and a novel mutation T242I, all other mutations (including D268H and three novel S23R, D215H and I351T mutations) were found only in single families in single alleles. A search for this disorder should be included in the screening program of all infants with unexplained neonatal seizures, severe infantile epileptic encephalopathy, developmental delay, hypotonia, and/or autistic features.

  10. Clinical features of Candidiasis in patients with inherited interleukin 12 receptor β1 deficiency.

    Science.gov (United States)

    Ouederni, Monia; Sanal, Ozden; Ikinciogullari, Aydan; Tezcan, Ilhan; Dogu, Figen; Sologuren, Ithaisa; Pedraza-Sánchez, Sigifredo; Keser, Melike; Tanir, Gonul; Nieuwhof, Chris; Colino, Elena; Kumararatne, Dinakantha; Levy, Jacov; Kutukculer, Necil; Aytekin, Caner; Herrera-Ramos, Estefanía; Bhatti, Micah; Karaca, Neslihan; Barbouche, Ridha; Broides, Arnon; Goudouris, Ekaterini; Franco, José Luis; Parvaneh, Nima; Reisli, Ismail; Strickler, Alexis; Shcherbina, Anna; Somer, Ayper; Segal, Anthony; Angel-Moreno, Alfonso; Lezana-Fernandez, José Luis; Bejaoui, Mohamed; Bobadilla-Del Valle, Miriam; Kachboura, Salem; Sentongo, Timothy; Ben-Mustapha, Imen; Bustamante, Jacinta; Picard, Capucine; Puel, Anne; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent; Rodríguez-Gallego, Carlos

    2014-01-01

    Interleukin 12Rβ1 (IL-12Rβ1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

  11. Usefulness of Iron Deficiency Correction in Management of Patients With Heart Failure [from the Registry Analysis of Iron Deficiency-Heart Failure (RAID-HF) Registry].

    Science.gov (United States)

    Wienbergen, Harm; Pfister, Otmar; Hochadel, Matthias; Michel, Stephan; Bruder, Oliver; Remppis, Björn Andrew; Maeder, Micha Tobias; Strasser, Ruth; von Scheidt, Wolfgang; Pauschinger, Matthias; Senges, Jochen; Hambrecht, Rainer

    2016-12-15

    Iron deficiency (ID) has been identified as an important co-morbidity in patients with heart failure (HF). Intravenous iron therapy reduced symptoms and rehospitalizations of iron-deficient patients with HF in randomized trials. The present multicenter study investigated the "real-world" management of iron status in patients with HF. Consecutive patients with HF and ejection fraction ≤40% were recruited and analyzed from December 2010 to October 2015 by 11 centers in Germany and Switzerland. Of 1,484 patients with HF, iron status was determined in only 923 patients (62.2%), despite participation of the centers in a registry focusing on ID and despite guideline recommendation to determine iron status. In patients with determined iron status, a prevalence of 54.7% (505 patients) for ID was observed. Iron therapy was performed in only 8.5% of the iron-deficient patients with HF; 2.6% were treated with intravenous iron therapy. The patients with iron therapy were characterized by a high rate of symptomatic HF and anemia. In conclusion, despite strong evidence of beneficial effects of iron therapy on symptoms and rehospitalizations, diagnostic and therapeutic efforts on ID in HF are low in the actual clinical practice, and the awareness to diagnose and treat ID in HF should be strongly enforced. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency

    DEFF Research Database (Denmark)

    Thomsen, J L; Nielsen, C V; Palmqvist, D F

    2015-01-01

    if neuromuscular monitoring was not applied before awakening. METHODS: We retrospectively included patients referred to the Danish Cholinesterase Research Unit between 2004 and 2012 on suspicion of BChE deficiency. We collected data on genotype, BChE activity, neuromuscular blocking agents administered......, neuromuscular monitoring, and postoperative respiratory complications, defined as arterial oxygen desaturation ... paralysed. RESULTS: We included 123 patients. Neuromuscular monitoring was applied before awakening in 48 (39%) patients. A nerve stimulator was never used or only after attempted awakening in the remaining 75 (61%) patients. Premature awakening occurred in 75 (100%) and 14 (29%) of the unmonitored...

  13. High rate of CAD gene amplification in human cells deficient in MLH1 or MSH6

    Science.gov (United States)

    Chen, Sihong; Bigner, Sandra H.; Modrich, Paul

    2001-01-01

    MutS and MutL homologs have been implicated in multiple genetic stabilization pathways. The activities participate in the correction of DNA biosynthetic errors, are involved in cellular responses to certain types of DNA damage, and serve to ensure the fidelity of genetic recombination. We show here that the rate of CAD (carbamyl-P synthetase/aspartate transcarbamylase/dihydroorotase) gene amplification is elevated 50- to 100-fold in human cell lines deficient in MLH1 or MSH6, as compared with mismatch repair-proficient control cells. Fluorescence in situ hybridization indicates that these amplification events are the probable consequence of unequal sister chromatid exchanges involving chromosome 2, as well as translocation events involving other chromosomes. These results implicate MutSα and MutLα in the suppression of gene amplification and suggest that defects in this genetic stabilization function may contribute to the cancer predisposition associated with mismatch repair deficiency. PMID:11717437

  14. Characterizing T Cells in SCID Patients Presenting with Reactive or Residual T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Atar Lev

    2012-01-01

    Full Text Available Introduction. Patients with severe combined immunodeficiency (SCID may present with residual circulating T cells. While all cells are functionally deficient, resulting in high susceptibility to infections, only some of these cells are causing autoimmune symptoms. Methods. Here we compared T-cell functions including the number of circulating CD3+ T cells, in vitro responses to mitogens, T-cell receptor (TCR repertoire, TCR excision circles (TREC levels, and regulatory T cells (Tregs enumeration in several immunodeficinecy subtypes, clinically presenting with nonreactive residual cells (MHC-II deficiency or reactive cells. The latter includes patients with autoreactive clonal expanded T cell and patients with alloreactive transplacentally maternal T cells. Results. MHC-II deficient patients had slightly reduced T-cell function, normal TRECs, TCR repertoires, and normal Tregs enumeration. In contrast, patients with reactive T cells exhibited poor T-cell differentiation and activity. While the autoreactive cells displayed significantly reduced Tregs numbers, the alloreactive transplacentally acquired maternal lymphocytes had high functional Tregs. Conclusion. SCID patients presenting with circulating T cells show different patterns of T-cell activity and regulatory T cells enumeration that dictates the immunodeficient and autoimmune manifestations. We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency.

  15. Recurrent Cerebral Infarctions in a Young Patient: Combined Protein C and S Deficiencies

    International Nuclear Information System (INIS)

    Sultan, A.; Malik, I. H.

    2013-01-01

    The possible etiologies of cerebral infarcts in young patients often present as diagnostic dilemmas as compared to older patients. Recently, deficiencies of fibrinolytic factors have emerged as an important etiology of stroke in the young population. Thrombophilic factors have been implicated in approximately 4 - 8% of the young strokes worldwide. Combined protein C and S deficiencies is a rare cause of recurrent ischaemic stroke in young population. Only a few sporadic cases have been reported in the literature. We are reporting a case of combined protein C and S deficiencyrelated recurrent ischaemic stroke in an 18 years old girl. Early diagnosis and targeted therapeutic management can help such patients to prevent recurrent thrombotic episodes. (author)

  16. Anaesthetic management in patients with glucose-6-phosphate dehydrogenase deficiency undergoing neurosurgical procedures

    Directory of Open Access Journals (Sweden)

    Sebastian Valiaveedan

    2011-01-01

    Full Text Available Glucose-6-phosphate dehydrogenase (G-6-PD deficiency is an X-linked recessive enzymopathy responsible for acute haemolysis following exposure to oxidative stress. Drugs which induce haemolysis in these patients are often used in anaesthesia and perioperative pain management. Neurosurgery and few drugs routinely used during these procedures are known to cause stress situations. Associated infection and certain foodstuffs are also responsible for oxidative stress. Here, we present two patients with G-6-PD deficiency who underwent uneventful neurosurgical procedures. The anaesthetic management in such patients should focus on avoiding the drugs implicated in haemolysis, reducing the surgical stress with adequate analgesia, and monitoring for and treating the haemolysis, should it occur.

  17. Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis.

    Science.gov (United States)

    Cardaci, Simone; Zheng, Liang; MacKay, Gillian; van den Broek, Niels J F; MacKenzie, Elaine D; Nixon, Colin; Stevenson, David; Tumanov, Sergey; Bulusu, Vinay; Kamphorst, Jurre J; Vazquez, Alexei; Fleming, Stewart; Schiavi, Francesca; Kalna, Gabriela; Blyth, Karen; Strathdee, Douglas; Gottlieb, Eyal

    2015-10-01

    Succinate dehydrogenase (SDH) is a heterotetrameric nuclear-encoded complex responsible for the oxidation of succinate to fumarate in the tricarboxylic acid cycle. Loss-of-function mutations in any of the SDH genes are associated with cancer formation. However, the impact of SDH loss on cell metabolism and the mechanisms enabling growth of SDH-defective cells are largely unknown. Here, we generated Sdhb-ablated kidney mouse cells and used comparative metabolomics and stable-isotope-labelling approaches to identify nutritional requirements and metabolic adaptations to SDH loss. We found that lack of SDH activity commits cells to consume extracellular pyruvate, which sustains Warburg-like bioenergetic features. We further demonstrated that pyruvate carboxylation diverts glucose-derived carbons into aspartate biosynthesis, thus sustaining cell growth. By identifying pyruvate carboxylase as essential for the proliferation and tumorigenic capacity of SDH-deficient cells, this study revealed a metabolic vulnerability for potential future treatment of SDH-associated malignancies.

  18. Prevalence of factor VII deficiency and molecular characterization of the F7 gene in Brazilian patients.

    Science.gov (United States)

    Rodrigues, Dalva N; Siqueira, Lucia H; Galizoni, Andréa M; Arruda, Valder R; Annichino-Bizzacchi, Joyce M

    2003-04-01

    The prevalence of factor VII (FVII) deficiency in 267 Brazilian patients was estimated to be 4.1%, including one patient with significant bleeding, five with minor bleeding and five patients asymptomatic. Only one novel mutation 8926G F7 polymorphisms and FVII activity were found in these patients, as those with higher levels of FVII activity presented the genotype described in the literature as related to reduced FVII activity. As the R304Q mutation was the most frequent in these patients, and may be associated with an asymptomatic form of the disease, particularly in Blacks, we examined this mutation and FVII activity in 49 Blacks and 49 Caucasian blood donors with no clinical bleeding. None of the individuals showed the R304Q mutation, and FVII activity was normal in all of them, thus indicating that FVII deficiency is not common in normal individuals of these two ethnic groups in Brazil. This is the first study in South America to examine the prevalence and molecular basis of FVII deficiency, including the description of a novel mutation.

  19. Intravenous Iron Repletion Does Not Significantly Decrease Platelet Counts in CKD Patients with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Neville R. Dossabhoy

    2013-01-01

    Full Text Available Purpose. We sought to investigate the effect of IV iron repletion on platelet (PLT counts in CKD patients with iron deficiency anemia (IDA. Methods. We conducted a retrospective chart review, including all patients with CKD and IDA who were treated with iron dextran total dose infusion (TDI between 2002 and 2007. Patient demographics were noted, and laboratory values for creatinine, hemoglobin (Hgb, iron stores and PLT were recorded pre- and post-dose. Results. 153 patients received a total of 251 doses of TDI (mean ± SD = 971 ± 175 mg; age years and Creatinine  mg/dL. All CKD stages were represented (stage 4 commonest. Hgb and Fe stores improved post-TDI (. There was a very mild decrease in PLT (pre-TDI 255 versus post-TDI 244, . The mild reduction in PLT after TDI remained non-significant ( when data was stratified by molecular weight (MW of iron dextran used (low versus high, as well as by dose administered (<1000 versus ≥1000 mg. Linear regression analysis between pre-dose PLT and Tsat and Fe showed R2 of 0.01 and 0.04, respectively. Conclusion. Correction of iron deficiency did not significantly lower PLT in CKD patients, regardless of MW or dose used. Correlation of PLT to severity of iron deficiency was very weak.

  20. Effects of LAR and PTP-BL phosphatase deficiency on adult mouse retinal cells activated by lens injury.

    NARCIS (Netherlands)

    Lorber, B.; Hendriks, W.J.A.J.; Zee, C.E.E.M. van der; Berry, M.; Logan, A.

    2005-01-01

    Using intact and lens-lesioned wildtype, leucocyte common antigen-related phosphatase deficient (LARDeltaP) and protein tyrosine phosphatase (PTP)-BAS-like phosphatase deficient (PTP-BLDeltaP) mice, we have evaluated the role of LAR and PTP-BL in retinal ganglion cell survival and neuritogenesis,

  1. Zinc Deficiency Induces Apoptosis via Mitochondrial p53- and Caspase-Dependent Pathways in Human Neuronal Precursor Cells

    Science.gov (United States)

    Seth, Rohit; Corniola, Rikki S.; Gower-Winter, Shannon D.; Morgan, Thomas J., Jr.; Bishop, Brian; Levenson, Cathy W.

    2015-01-01

    Previous studies have shown that zinc deficiency leads to apoptosis of neuronal precursor cells in vivo and in vitro. In addition to the role of p53 as a nuclear transcription factor in zinc deficient cultured human neuronal precursors (NT-2), we have now identified the translocation of phosphorylated p53 to the mitochondria and p53-dependent…

  2. Dexmedetomidine-based intravenous anesthesia of a pediatric patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency: A case report.

    Science.gov (United States)

    Takahashi, Nanae; Ogawa, Takashi; Wajima, Zen'ichiro; Omi, Akibumi

    2017-05-01

    Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, resulting in deficits in nicotinamide adenine dinucleotide phosphate production, an important intracellular antioxidant enzyme. G6PD-deficient subjects present with a susceptibility of erythrocytes to oxidative stress and hemolysis, and should avoid drugs or stressors that have oxidative actions. Dexmedetomidine is an anesthetic agent with antioxidant actions. A 5-year-old boy with G6PD deficiency. The patient was diagnosed with G6PD deficiency at birth. His red blood cell levels were indicating Class II G6PD activity by the World Health Organization (WHO) classification, but had no history of hemolytic anemia. Because of the patient's anxiety and hyperactivity prior to an operation for upper labial frenum resection, we performed perioperative management using intravenous sedation with dexmedetomidine, which provides upper airway patency and has an antioxidant action. There was no abnormal breathing observed during anesthesia, and arousal was smooth with stable hemodynamics. The patient had no symptoms of hemolytic anemia up to 1 week postsurgery. Antioxidant sedatives such as dexmedetomidine may be useful for reducing the risk of hemolysis after surgery in infant G6PD deficiency cases.

  3. Work-Family Conflict, Psychological Distress and Sleep Deficiency Among Patient Care Workers

    Science.gov (United States)

    Jacobsen, Henrik Børsting; Reme, Silje Endresen; Sembajwe, Grace; Hopcia, Karen; Stoddard, Anne M.; Kenwood, Christopher; Stiles, Tore C.; Sorensen, Glorian; Buxton, Orfeu M.

    2015-01-01

    Objectives There is a well-established link between psychological distress, work-related stress and sleep. The aim of this study was to test the hypothesis that work-family conflict was associated with sleep deficiency both cross-sectionally and longitudinally while controlling for potential covariates. Methods In this two-phase study, a workplace health survey was collected from a cohort of patient care workers (n=1,572) at two large hospitals. Follow-up was collected nearly two years later in a subsample (n=102). Self-reported measures included work-family conflict, socio-demographics, workplace factors, psychological distress, and outcomes of sleep duration, sleep insufficiency, and sleep maintenance. Bivariate associations (Pwork-family conflict were significantly associated with sleep deficiency, short sleep duration and perceived sleep insufficiency, but not with sleep maintenance problems. Higher levels of work-family conflict also predicted sleep insufficiency at follow-up nearly two years later. None of the other variables were associated with sleep outcomes longitudinally. Conclusion This is the first study to determine the predictive and cross-sectional associations of work-family conflict on sleep deficiency, also controlling for other measures of job stress and psychological distress. The results indicate that future interventions on sleep deficiency in patient care workers should include a specific focus on work-family conflict. PMID:25000547

  4. Gastric emptying in patients with vitamin B{sub 12} deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Yagci, Muenci; Yamac, Kadri; Acar, Kadir; Haznedar, Rauf [Department of Hematology, Gazi Medical School (Turkey); Cingi, Elif; Kitapci, Mehmet [Department of Nuclear Medicine, Gazi Medical School (Turkey)

    2002-09-01

    The clinical presentation of patients with vitamin B{sub 12} deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B{sub 12} deficiency. The aim of this study was to evaluate the effect of vitamin B{sub 12} deficiency on autonomic nervous system function by studying gastric emptying times (T{sub 1/2}). Twenty patients with newly diagnosed vitamin B{sub 12} deficiency and 12 control patients with gastritis and normal vitamin B{sub 12} levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B{sub 12} replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T{sub 1/2} in patients before and after treatment and in controls were 103.83{+-}48.80 min, 90.00{+-}17.29 min and 74.55{+-}8.52 min, respectively. The difference in mean gastric emptying T{sub 1/2} between patients before treatment and controls was statistically significant (P<0.01). The statistically significant difference persisted after vitamin B{sub 12} treatment (P<0.05), though mean gastric emptying T{sub 1/2} was somewhat shorter. There were no positive or negative correlations between gastric emptying T{sub 1/2} and the following parameters: haemoglobin, vitamin B{sub 12} level and Helicobacter pylori positivity. In conclusion, gastric emptying T{sub 1/2} was prolonged in patients with vitamin B{sub 12} deficiency and this prolongation was not corrected after vitamin B{sub 12} replacement therapy. Although autonomic nervous system dysfunction due to vitamin B{sub 12} deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon

  5. Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

    Directory of Open Access Journals (Sweden)

    M. Sambucci

    2013-01-01

    Full Text Available T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosylation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose polymerases (PARPs. Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases.

  6. Smith-Magenis Syndrome Patients Often Display Antibody Deficiency but Not Other Immune Pathologies.

    Science.gov (United States)

    Perkins, Tiffany; Rosenberg, Jacob M; Le Coz, Carole; Alaimo, Joseph T; Trofa, Melissa; Mullegama, Sureni V; Antaya, Richard J; Jyonouchi, Soma; Elsea, Sarah H; Utz, Paul J; Meffre, Eric; Romberg, Neil

    Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder associated with recurrent otitis. Most SMS cases result from heterozygous interstitial chromosome 17p11.2 deletions that encompass not only the intellectual disability gene retinoic acid-induced 1 but also other genes associated with immunodeficiency, autoimmunity, and/or malignancy. The goals of this study were to describe the immunological consequence of 17p11.2 deletions by determining the prevalence of immunological diseases in subjects with SMS and by assessing their immune systems via laboratory methods. We assessed clinical histories of 76 subjects with SMS with heterozygous 17p11.2 deletions and performed in-depth immunological testing on 25 representative cohort members. Laboratory testing included determination of serum antibody concentrations, vaccine titers, and lymphocyte subset frequencies. Detailed reactivity profiles of SMS serum antibodies were performed using custom-made antigen microarrays. Of 76 subjects with SMS, 74 reported recurrent infections including otitis (88%), pneumonia (47%), sinusitis (42%), and gastroenteritis (34%). Infections were associated with worsening SMS-related neurobehavioral symptoms. The prevalence of autoimmune and atopic diseases was not increased. Malignancy was not reported. Laboratory evaluation revealed most subjects with SMS to be deficient of isotype-switched memory B cells and many to lack protective antipneumococcal antibodies. SMS antibodies were not more reactive than control antibodies to self-antigens. Patients with SMS with heterozygous 17p.11.2 deletions display an increased susceptibility to sinopulmonary infections, but not to autoimmune, allergic, or malignant diseases. SMS sera display an antibody reactivity profile favoring neither recognition of pathogen-associated antigens nor self-antigens. Prophylactic strategies to prevent infections may also provide neurobehavioral benefits to selected patients with SMS. Copyright © 2017

  7. Micronutrient Deficiencies in Patients Candidate for Bariatric Surgery: A Prospective, Preoperative Trial of Screening, Diagnosis, and Treatment.

    Science.gov (United States)

    Schiavo, Luigi; Scalera, Giuseppe; Pilone, Vincenzo; De Sena, Gabriele; Capuozzo, Vincenza; Barbarisi, Alfonso

    2016-05-10

    Bariatric surgery candidates often show preoperative micronutrient deficiency. Although it is documented that a comprehensive micronutrient assessment should be conducted preoperatively to correct the deficiencies before surgery, no previous studies have been effective in correcting deficiencies in sufficient time prior to surgery. Our aim was to identify micronutrient deficiencies preoperatively and correct them before surgery. 50 patients (18 female, 32 male) scheduled for bariatric surgery were assessed for micronutrient status 20 weeks prior to surgery. Baseline levels of vitamin B12, folic acid, 25-vitamin D, vitamin C, vitamin A, vitamin E, iron, zinc, magnesium, and selenium were measured. Data were compared with accepted clinical cutoff values. Patients found to have one or more micronutrient deficiencies were instructed to take daily micronutrient supplements specially formulated for obese patients and were evaluated every 5 weeks over a 20-week period. Nutrient intake was also evaluated before and after supplementation. Micronutrient deficiencies were observed in 40 patients (80 %, 13 female, 27 male). All 40 patients started prescribed supplementation immediately. 20 patients (10 female, 10 male) completed a follow-up at 20 weeks. Herein we found that 10 weeks of preoperative micronutrient supplementation is capable of effectively treating micronutrient deficiencies in our candidates for bariatric surgery. Considering that: 1) no new medication was allowed during the study; 2) patients already under pharmacological treatment did not change their therapy; 3) no statistically differences in nutrient intake were observed before and after the supplementation, we are confident to attribute the improvements in patients' micronutrient status directly to the supplement.

  8. Transplantation of CD51+Stem Leydig Cells: A New Strategy for the Treatment of Testosterone Deficiency.

    Science.gov (United States)

    Zang, Zhi Jun; Wang, Jiancheng; Chen, Zhihong; Zhang, Yan; Gao, Yong; Su, Zhijian; Tuo, Ying; Liao, Yan; Zhang, Min; Yuan, Qunfang; Deng, Chunhua; Jiang, Mei Hua; Xiang, Andy Peng

    2017-05-01

    Stem Leydig cell (SLC) transplantation could provide a new strategy for treating the testosterone deficiency. Our previous study demonstrated that CD51 (also called integrin αv) might be a putative cell surface marker for SLCs, but the physiological function and efficacy of CD51 + SLCs treatment remain unclear. Here, we explore the potential therapeutic benefits of CD51 + SLCs transplantation and whether these transplanted cells can be regulated by the hypothalamic-pituitary-gonadal (HPG) axis. CD51 + cells were isolated from the testes of 12-weeks-old C57BL/6 mice, and we showed that such cells expressed SLC markers and that they were capable of self-renewal, extensive proliferation, and differentiation into multiple mesenchymal cell lineages and LCs in vitro. As a specific cytotoxin that eliminates Leydig cells (LCs) in adult rats, ethane dimethanesulfonate (EDS) was used to ablate LCs before the SLC transplantation. After being transplanted into the testes of EDS-treated rats, the CD51 + cells differentiated into mature LCs, and the recipient rats showed a partial recovery of testosterone production and spermatogenesis. Notably, a testosterone analysis revealed a circadian rhythm of testosterone secretion in cell-transplanted rats, and these testosterone secretions could be suppressed by decapeptyl (a luteinizing hormone-releasing hormone agonist), suggesting that the transplanted cells might be regulated by the HPG axis. This study is the first to demonstrate that CD51 + SLCs can restore the neuroendocrine regulation of testicular function by physiologically recovering the expected episodic changes in diurnal testosterone serum levels and that SLC transplantation may provide a new tool for the studies of testosterone deficiency treatment. Stem Cells 2017;35:1222-1232. © 2017 AlphaMed Press.

  9. Reduction of nitroxide free radical by normal and G6PD deficient red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Branca, M.; Denurra, T.; Turrini, F. (dell' Universita di Sassari (Italy))

    1988-01-01

    The electron spin resonance signal of Tempol decays in the presence of red cells. The decay is due to reduction of oxidant, paramagnetic nitroxide group by the metabolic activity of the red cell. In normal red cells, GSH level was stable and Tempol reduction rate followed a first-order kinetics. In G6PD-deficient red cells, GSH dropped and Tempol reduction rate was slower and followed a second-order kinetics. In normal red cells, diamide reversibly oxidized GSH. First-order kinetics of Tempol reduction rate was attained after a delay time proportional to the diamide concentration and corresponding to the full regeneration of GSH. In diamide-treated G6PD deficient, and in NEM-treated, normal red cells, irreversible disappearance of GSH was followed by irreversible dose-dependent decrease in Tempol reduction rate. A correlation between GSH levels and Tempol reduction rate was observed. A correlation was also established between Tempol reduction rate and stimulation of pentosephosphate shunt activity.

  10. Severe deficiency of glycoprotein VI in a patient with gray platelet syndrome.

    Science.gov (United States)

    Nurden, Paquita; Jandrot-Perrus, Martine; Combrié, Robert; Winckler, Joelle; Arocas, Veronique; Lecut, Christelle; Pasquet, Jean-Max; Kunicki, Thomas J; Nurden, Alan T

    2004-07-01

    We report a novel case of gray platelet syndrome (GPS) where a severe deficiency of the platelet collagen receptor, glycoprotein (GP) VI, accompanies classical symptoms of a low platelet count and platelets lacking alpha-granules. Dense granules were normally present. Platelet aggregation with collagen was severely decreased, as was the response to convulxin (Cvx), a GPVI agonist. Quantitative analysis of GPVI using fluorescein isothiocyanate (FITC)-Cvx in flow cytometry showed its virtual absence on the patient's platelets. The GPVI deficiency was confirmed using monoclonal antibodies in Western blotting and in immunogold labeling on frozen thin sections where internal pools of GPVI were confirmed for normal platelets. The Fc receptor gamma-chain, constitutively associated with GPVI in normal platelets, was present in subnormal amounts, and the phospholipase C gamma 2-dependent activation pathway appeared to function normally. No autoantibodies to GPVI were found in the patient's serum using monoclonal antibody immobilization of platelet antigen (MAIPA). Sequencing of coding regions of the GPVI gene failed to show abnormalities, and mRNA for GPVI was present in the patient's platelets, pointing to a probable acquired defect in GPVI expression. Our results may provide a molecular explanation for the subgroup of patients with severely deficient collagen-induced platelet aggregation as previously described for GPS in the literature.

  11. Intrafamilial variability in the phenotypic expression of adenylosuccinate lyase deficiency: a report on three patients.

    Science.gov (United States)

    Edery, Patrick; Chabrier, Stéphane; Ceballos-Picot, Irène; Marie, Sandrine; Vincent, Marie-Françoise; Tardieu, Marc

    2003-07-15

    We report on the striking variable expression of adenylosuccinate lyase (ADSL) deficiency in three patients belonging to a family which originates from Portugal. ADSL deficiency is a rare autosomal recessive disorder of the de novo purine synthesis which results in accumulation of succinylpurines in body fluids. As a result, patients may have variable combinations of psychomotor retardation and/or regression, seizures, autistic features and cerebellar vermis hypoplasia. However, intrafamilial variable expression of the phenotype has not been documented to date in this disease and is not commonly observed in metabolic disorders. Here, while the proband had marked psychomotor regression and progressive cerebellar vermis atrophy, the other two affected patients presented mainly autistic features. Mutation analysis of the ADSL gene revealed the presence of a homozygous R426H mutation in this family. Finally, although ADSL deficiency is a rare disorder, this diagnosis should be considered and assessed using a simple urinary screening method for the presence of succinylpurines in any patient with mental retardation of unexplained origin. Copyright 2003 Wiley-Liss, Inc.

  12. High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients.

    Science.gov (United States)

    Mueller, Nicolas J; Fux, Christoph A; Ledergerber, Bruno; Elzi, Luigia; Schmid, Patrick; Dang, Thanh; Magenta, Lorenzo; Calmy, Alexandra; Vergopoulos, Athanasios; Bischoff-Ferrari, Heike A

    2010-05-15

    To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis. Retrospective assessment of vitamin D levels by season and initiation of combined antiretroviral therapy (cART). 25(OH)D was measured in 211 HIV-positive patients: samples were taken before initiation of cART from February to April or from August to October as well as 12 (same season) and 18 months (alternate season) after starting cART. 1,25-Dihydroxyvitamin D [1,25(OH)2D] was measured in a subset of 74 patients. Multivariable analyses included season, sex, age, ethnicity, BMI, intravenous drug use (IDU), renal function, time since HIV diagnosis, previous AIDS, CD4 cell count and cART, in particular nonnucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF) use. At baseline, median 25(OH)D levels were 37 (interquartile range 20-49) nmol/l in spring and 57 (39-74) nmol/l in the fall; 25(OH)D deficiency less than 30 nmol/l was more prevalent in spring (42%) than in fall (14%), but remained unchanged regardless of cART exposure. In multivariable analysis, 25(OH)D levels were higher in white patients and those with a longer time since HIV diagnosis and lower in springtime measurements and in those with active IDU and NNRTI use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. Hepatitis C seropositivity, previous AIDS and higher CD4 cell counts correlated with lower 1,25(OH)2D levels, whereas BMI and TDF use were associated with higher levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase. Based on the high rate of vitamin D deficiency in HIV-positive patients, systematic screening with consideration of seasonality is warranted. The impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further attention.

  13. Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Patrick C Lee

    2016-01-01

    Full Text Available Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.

  14. The prevalence of vitamin D deficiency in consecutive new patients seen over a 6-month period in general rheumatology clinics.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    The objectives of this study are to assess: (a) the prevalence of vitamin D deficiency among new patients attending rheumatology outpatient departments, (b) the age profile of these low vitamin D patients and (c) whether any diagnostic category had a particularly high number of vitamin D-deficient patients. All new patients seen consecutively in general rheumatology clinics between January to June 2007 inclusive were eligible to partake in this study, and 231 out of 264 consented to do so. Parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium, phosphate, albumin and alkaline phosphatase levels were measured. We defined vitamin D deficiency as <\\/=53 nmol\\/l and severe deficiency as <\\/=25 nmol\\/l. Overall, 70% of 231 patients had vitamin D deficiency, and 26% had severe deficiency. Sixty-five percent of patients aged >\\/=65 and 78% of patients aged <\\/=30 years had low vitamin D levels. Vitamin D deficiency in each diagnostic category was as follows: (a) inflammatory joint diseases\\/connective tissue diseases (IJD\\/CTD), 69%; (b) soft tissue rheumatism, 77%; (c) osteoarthritis, 62%; (d) non-specific musculoskeletal back pain, 75% and (e) osteoporosis, 71%. Seasonal variation of vitamin D levels was noted in all diagnostic groups apart from IJD\\/CTD group, where the degree of vitamin D deficiency persisted from late winter to peak summer. Very high prevalence of vitamin D deficiency was noted in all diagnostic categories (p = 0.006), and it was independent of age (p = 0.297). The results suggest vitamin D deficiency as a possible modifiable risk factor in different rheumatologic conditions, and its role in IJD\\/CTD warrants further attention.

  15. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

    OpenAIRE

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos Junior, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; Souza, Altay Alves Lino de; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of <...

  16. Prevalence of factor XII (Hageman factor) deficiency among 426 patients with coronary heart disease awaiting cardiac surgery.

    Science.gov (United States)

    Halbmayer, W M; Haushofer, A; Radek, J; Schön, R; Deutsch, M; Fischer, M

    1994-05-01

    Several case reports of myocardial infarction in patients with factor XII deficiency have been published. In the present study we investigated the prevalence of this condition. Factor XII activity (one-stage clotting assay), fibrinogen (derived method), and lipoprotein (a) (enzyme-linked immunosorbent assay) were measured in the plasma of 426 consecutive patients with coronary heart disease awaiting cardiac surgery. Among the 426 patients, 44 (10.3%) were found to be moderately deficient in factor XII (factor XII activity 17-50%, antigen 15-57%). The prevalence of factor XII deficiency was significantly higher (P < 0.0001) among patients with coronary heart disease than among 300 healthy blood donors (2.3%). Among coronary heart disease patients with this deficiency, elevated levels of fibrinogen, lipoprotein (a), and blood pressure were no more prevalent than in those without the deficiency; nor were cigarette smoking or a positive family history of thromboembolism more prevalent. Coronary heart disease patients showed a 10% prevalence of factor XII deficiency. However, the pattern of atherosclerotic risk factors did not differ between patients with or without the deficiency.

  17. PREVALENCE OF TESTOSTERONE DEFICIENCY IN PATIENTS OF DIABETES MELLITUS LESS THAN 40 YEARS OF AGE

    Directory of Open Access Journals (Sweden)

    Praveen K

    2016-01-01

    Full Text Available BACKGROUND Diabetes mellitus is common endocrine disorder which involves multiple organs and leads to significant morbidity and mortality due to accompanying complications. Erectile dysfunction, reduced libido, orgasmic dysfunction, and retrograde ejaculation are established complications found with variable prevalence in men with diabetes. METHODOLOGY In the present study, total 90 male patients of diabetes mellitus of age below 40 years were taken from medical outpatient department and indoor patients of medical wards of a tertiary care teaching hospital of South Delhi. They were evaluated for complains regarding sexual dysfunction. Hormonal assays of serum free testosterone, LH, FSH, C-peptide, HbA1c and lipid profile were carried out in all patients. RESULT Present study shows that testosterone deficiency is quite common in young diabetic patients. Low serum free testosterone was more common in type 2 diabetes as compared to type 1 diabetes (38.46% Vs 29.41%. BMI has significant effect on serum free testosterone levels. Patients with higher BMI had negative correlation to free testosterone although testosterone deficiency was also seen in few lean patients. High serum triglyceride and low serum HDL were seen more frequently in patients with low free testosterone. CONCLUSION This study reveals that hypogonadism is not a rarity even at initial stages of diabetes. This study, although small, highlights importance of assessment of young diabetic patients for sexual dysfunction and hypogonadism.

  18. Rapid eye movement sleep behaviour disorder in patients with narcolepsy is associated with hypocretin-1 deficiency

    DEFF Research Database (Denmark)

    Knudsen, Stine; Gammeltoft, Steen; Jennum, Poul J

    2010-01-01

    Rapid eye movement sleep behaviour disorder is characterized by dream-enacting behaviour and impaired motor inhibition during rapid eye movement sleep. Rapid eye movement sleep behaviour disorder is commonly associated with neurodegenerative disorders, but also reported in narcolepsy with cataplexy....... Most narcolepsy with cataplexy patients lack the sleep-wake, and rapid eye movement sleep, motor-regulating hypocretin neurons in the lateral hypothalamus. In contrast, rapid eye movement sleep behaviour disorder and hypocretin deficiency are rare in narcolepsy without cataplexy. We hypothesized...... that rapid eye movement sleep behaviour disorder coexists with cataplexy in narcolepsy due to hypocretin deficiency. In our study, rapid eye movement sleep behaviour disorder was diagnosed by the International Classification of Sleep Disorders (2nd edition) criteria in 63 narcolepsy patients with or without...

  19. Protocol for Dental Management in a Patient with Glucose6-Phosphate Dehydrogenase Deficiency

    Directory of Open Access Journals (Sweden)

    Ramachandran Anil Kumar

    2017-10-01

    Full Text Available Glucose-6-Phosphate Dehydrogenase (G6PD enzyme deficiency is the most common inherited genetic disorder affecting RBCs in humans. The disorder is characterised by inability of RBC to maintain a balanced redox state when challenged by oxidative stresses like drugs, infections and certain food substances leading to severe haemolytic anaemia which complicates any therapeutic management in these patients. This article reports on a successful endodontic management of a 36-year-old class III G6PD deficient male patient with deep carious lesion in left mandibular first molar tooth (36. Considering there is no protocol precedence in dental literature, in consultation with the physician/haemotologist a three step protocol for safe and efficient dental management is proposed.

  20. Treatment of chronic portal-systemic encephalopathy with lactose in lactase-deficient patients.

    Science.gov (United States)

    Uribe, M; Márquez, M A; García-Ramos, G; Escobedo, V; Murillo, H; Guevara, L; Lisker, R

    1980-12-01

    A controlled cross-over clinical comparison of lactose (50 g twice a day) versus neomycin (3 g/day) plus milk of magnesia, was carried out in ten cirrhotic patients with chronic portal-systemic encephalopathy and documented lactase deficiency. Serial semiquantitative assessments were done including: mental state, asterixis, number connection test, electroencephalogram, and blood ammonia levels. No patient developed deep coma while ingesting either lactose or neomycin plus milk of magnesia. However, a significant improvement of mental state, asterixis, number connection tests, and electroencephalograms was evident during lactose therapy. apart from mild diarrhea and bloating, no severe side effects were noticeable during lactose treatment. Based on these results, we propose lactose as a valuable alternate treatment of portal-systemic encephalopathy in lactase-deficient populations.

  1. High prevalence of vitamin D deficiency and its association with metabolic disorders in elderly patients

    OpenAIRE

    Małgorzata Koziarska-Rościszewska; Jacek Rysz; Mariusz Stępień

    2017-01-01

    Background . Vitamin D is considered to be an important co-factor of metabolic processes. However, the available data is ambiguous. Some data indicates an important role of vitamin D in adipocyte metabolism, and hence also in obesity – a well-known risk factor of diabetes mellitus and cardiovascular diseases (CVD). Objectives . To assess the prevalence of vitamin D deficiency and to evaluate the relationship between serum 25(OH)D concentration and metabolic disorders in elderly patients ...

  2. Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

    DEFF Research Database (Denmark)

    Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

    2002-01-01

    In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...... or placebo; and after a 12-month open phase of GH therapy. In the placebo group, insulin sensitivity and fat mass increased and lipid oxidation decreased, whereas glucose oxidation increased (p...

  3. A successful outcome of pregnancy in a patient with congenital antithrombin deficiency

    Directory of Open Access Journals (Sweden)

    Kovač Mirjana

    2011-01-01

    Full Text Available Background. Presence of inherited thrombophilia is an additional risk factor for maternal thromboembolism and certain adverse pregnancy outcomes, including recurrent fetal loss, placental abruption, intrauterine growth restriction and earlyonset severe preeclampsia. Pregnant women with thrombophilia, especially those with antithrombin (AT deficiency, are at high risk of both kinds of complications. Case report. We presented a pregnant women with congenital antithrombin deficiency in the first pregnancy, whose mother had had four times pregnancy-related deep vein thrombosis, and antithrombin deficiency. With the regular laboratory monitoring of hemostatic parameters and gynaecology surveillance including the follow-up of placental vascular flow, the whole pregnancy proceeded without complications. The prophylactic therapy with low molecular weight heparin was introduced from the 20th week of gestation and one dose of substitution therapy with antithrombin concentrate was administrated before delivery. Pregnancy and labour were terminated without complications at the 37th week of gestation, resulting in the delivery of a healthy male newborn of 3.6 kg body weight, 52 cm long, and with the Apgar scores of 9/10. Conclusion. A timely made diagnosis of thrombophilia, accompanied with regular obstetrics check-ups and follow-ups of hemostatic parameters during pregnancy, as well as the use of adequate prophylactic and substitution therapy, are the successful tools for the prevention of possible maternal complications and pregnancy itself in our patient with congenital AT deficiency.

  4. PREVALENCE OF VITAMIN D DEFICIENCY IN DIFFERENT GROUPS OF CHRONIC RENAL FAILURE PATIENTS.

    Directory of Open Access Journals (Sweden)

    Bistra T. Galunska

    2015-09-01

    Full Text Available Purpose: To determine and compare the vitamin D status of different groups CKD patients on hemodialysis, peritoneal dialysis, or no renal replacement therapy and to evaluate the effect of vitamin D therapy. Patients and Methods: This pilot study enrolled 40 consecutive CKD patients (21 men, 19 women divided into three groups: 15 CKD patients in 1,2,3,4 stage of the disease without renal replacement therapy (RRT; 10CKD patients on hemodialysis (HD and 15 CKD patients on peritoneal dialysis (PD, ten of which were on vitamin D therapy. Vitamin D status was determined by serum 25-xydroxyvitamin D (25OHD. Results: Ninety percent of patients were in vitamin D deficiency/insufficiency; and only 4 patients (10.0% reached 25OHD levels above 75nmol/L. The median 25OHD level was 31.15nmol/L (interquartile range: 16.67-48.33nmol/L.Tendency of worse vitamin D status in women than in men was observed. Higher 25OHD levels were found in pre-dialysis patients (median 44.81nmol/L, 25%-75% percentile 16.24-52.21nmol/L and lower in HD (median 31.15nmol/L, 25%-75% percentile 13.04-64.45nmol/L and PD patients (median 33.38nmol/L, 25%-75% percentile 23.15-48.49nmol/L, but the difference did not reach statistical significance. Better vitamin D status was found in the PD group of patients receiving vitamin D preparations (p<0.05. Conclusions: 25OHD deficiency/insufficiency is prevalent in renal failure patients with or without renal replacement therapy. It seems that vitamin D therapy improves the vitamin D status of PD patients. Further larger studies are needed to clarify the effect of specific type vitamin D therapy on serum 25OHD levels and clinical outcome in different groups of CKD patients.

  5. A clinical and cardiovascular survey of Ehlers-Danlos syndrome patients with complete deficiency of tenascin-X.

    NARCIS (Netherlands)

    Peeters, A.C.T.; Kucharekova, M.; Timmermans, J.; Berkmortel, F.W.P.J. van den; Boers, G.H.J.; Nováková, I.R.O.; Egging, D.; Heijer, M. den; Schalkwijk, J.

    2004-01-01

    BACKGROUND: We recently described a new autosomal recessive type of Ehlers-Danlos syndrome (EDS) based on a deficiency of the extracellular matrix protein tenascin-X (TNX). TNX-deficient patients have hypermobile joints, hyperextensible skin and show easy bruising. Because of the reported

  6. Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients.

    Science.gov (United States)

    Hollak, C E M; de Sonnaville, E S V; Cassiman, D; Linthorst, G E; Groener, J E; Morava, E; Wevers, R A; Mannens, M; Aerts, J M F G; Meersseman, W; Akkerman, E; Niezen-Koning, K E; Mulder, M F; Visser, G; Wijburg, F A; Lefeber, D; Poorthuis, B J H M

    2012-11-01

    Niemann-Pick disease (NPD) is a neurovisceral lysosomal storage disorder caused by acid sphingomyelinase (ASM) deficiency, which can be categorized as either Niemann-Pick disease type A [NPD-A], with progressive neurological disease and death in early childhood, or as Niemann-Pick disease type B [NPD-B], with a more variable spectrum of manifestations. Enzyme replacement therapy (ERT) with recombinant sphingomyelinase is currently studied as potential treatment for NPD-B patients. The objective of this study is to characterize the clinical features of patients with ASM deficiency in the Netherlands and Belgium with focus on the natural disease course of NPD-B patients. Prospective and retrospective data on ASM deficient patients were collected in The Netherlands and part of Belgium. Patients with NPD-B that could be followed prospectively were evaluated every 6-12 months for pulmonary function tests, 6 minute walk test (6 MWT), imaging (bone marrow infiltration measured by QCSI, organ volumes by MRI and CT scan of the lungs) and biochemical markers. Twenty-five patients with ASM deficiency were identified (13 males, 12 females, median age 13years, range 1-59 years). Nine patients had died at the time of the study, including four NPD-A patients at the age of 1,1, 2, 3 and five NPDB patents at the age of 5, 6, 43, 56 and 60 years. There was a high prevalence of homozygosity and compound heterozygosity for the common p.Arg608del mutation in 43% and 19% of NPD-B patients, respectively. In NPD-B patients, thrombocytopenia was present in most, while anemia and leucopenia were less common (33% and 6 % respectively). HDL cholesterol was reduced in most patients. Pulmonary disease was severe in several patients. Follow-up up to 11 years revealed a gradual decrease in platelet count. Detailed investigations in 6 NPD-B patients with follow-up in 4 patients revealed remarkable stable disease parameters up to 6 years, with some decline in pulmonary function and 6 MWT. Bone

  7. Akt1 deficiency diminishes skeletal muscle hypertrophy by reducing satellite cell proliferation.

    Science.gov (United States)

    Moriya, Nobuki; Miyazaki, Mitsunori

    2018-02-14

    Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate. In this study, female germline Akt1 knockout (KO) mice were used to examine whether Akt1 deficiency attenuates load-induced skeletal muscle hypertrophy through suppressing mTOR-dependent signaling and satellite cell proliferation. Akt1 KO mice showed a blunted hypertrophic response of skeletal muscle, with a diminished rate of satellite cell proliferation following mechanical overload. In contrast, Akt1 deficiency did not affect the load-induced activation of mTOR signaling and the subsequent enhanced rate of protein synthesis in skeletal muscle. These observations suggest that the load-induced activation of mTOR signaling occurs independently of Akt1 regulation and that Akt1 plays a critical role in regulating satellite cell proliferation during load-induced muscle hypertrophy.

  8. TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice

    Science.gov (United States)

    Rickard, James A; Anderton, Holly; Etemadi, Nima; Nachbur, Ueli; Darding, Maurice; Peltzer, Nieves; Lalaoui, Najoua; Lawlor, Kate E; Vanyai, Hannah; Hall, Cathrine; Bankovacki, Aleks; Gangoda, Lahiru; Wong, Wendy Wei-Lynn; Corbin, Jason; Huang, Chunzi; Mocarski, Edward S; Murphy, James M; Alexander, Warren S; Voss, Anne K; Vaux, David L; Kaiser, William J; Walczak, Henning; Silke, John

    2014-01-01

    SHARPIN regulates immune signaling and contributes to full transcriptional activity and prevention of cell death in response to TNF in vitro. The inactivating mouse Sharpin cpdm mutation causes TNF-dependent multi-organ inflammation, characterized by dermatitis, liver inflammation, splenomegaly, and loss of Peyer's patches. TNF-dependent cell death has been proposed to cause the inflammatory phenotype and consistent with this we show Tnfr1, but not Tnfr2, deficiency suppresses the phenotype (and it does so more efficiently than Il1r1 loss). TNFR1-induced apoptosis can proceed through caspase-8 and BID, but reduction in or loss of these players generally did not suppress inflammation, although Casp8 heterozygosity significantly delayed dermatitis. Ripk3 or Mlkl deficiency partially ameliorated the multi-organ phenotype, and combined Ripk3 deletion and Casp8 heterozygosity almost completely suppressed it, even restoring Peyer's patches. Unexpectedly, Sharpin, Ripk3 and Casp8 triple deficiency caused perinatal lethality. These results provide unexpected insights into the developmental importance of SHARPIN. DOI: http://dx.doi.org/10.7554/eLife.03464.001 PMID:25443632

  9. International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency

    OpenAIRE

    Farkas, H.; Martinez?Saguer, I.; Bork, K.; Bowen, T.; Craig, T.; Frank, M.; Germenis, A. E.; Grumach, A. S.; Luczay, A.; Varga, L.; Zanichelli, A.; Aberer, Werner; Andrejevic, Sladjana; Aygoeren?P?rs?n, Emel; Banerji, Alena

    2016-01-01

    BACKGROUND: The consensus documents published to date on hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE.METHODS: During an expert panel meeting that took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015 (www.haenet.hu), ped...

  10. Design of a novel integration-deficient lentivector technology that incorporates genetic and posttranslational elements to target human dendritic cells.

    Science.gov (United States)

    Tareen, Semih U; Kelley-Clarke, Brenna; Nicolai, Christopher J; Cassiano, Linda A; Nelson, Lisa T; Slough, Megan M; Vin, Chintan D; Odegard, Jared M; Sloan, Derek D; Van Hoeven, Neal; Allen, James M; Dubensky, Thomas W; Robbins, Scott H

    2014-03-01

    As sentinels of the immune system, dendritic cells (DCs) play an essential role in regulating cellular immune responses. One of the main challenges of developing DC-targeted therapies includes the delivery of antigen to DCs in order to promote the activation of antigen-specific effector CD8 T cells. With the goal of creating antigen-directed immunotherapeutics that can be safely administered directly to patients, Immune Design has developed a platform of novel integration-deficient lentiviral vectors that target and deliver antigen-encoding nucleic acids to human DCs. This platform, termed ID-VP02, utilizes a novel genetic variant of a Sindbis virus envelope glycoprotein with posttranslational carbohydrate modifications in combination with Vpx, a SIVmac viral accessory protein, to achieve efficient targeting and transduction of human DCs. In addition, ID-VP02 incorporates safety features in its design that include two redundant mechanisms to render ID-VP02 integration-deficient. Here, we describe the characteristics that allow ID-VP02 to specifically transduce human DCs, and the advances that ID-VP02 brings to conventional third-generation lentiviral vector design as well as demonstrate upstream production yields that will enable manufacturing feasibility studies to be conducted.

  11. Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.

    Science.gov (United States)

    Chen, Bee Chin; McGown, Ivan N; Thong, Meow Keong; Pitt, James; Yunus, Zabedah M; Khoo, Teck Beng; Ngu, Lock Hock; Duley, John A

    2010-12-01

    Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).

  12. Iodine deficiency and subclinical hypothyroidism are common in cystic fibrosis patients.

    Science.gov (United States)

    Naehrlich, Lutz; Dörr, Helmuth-Günther; Bagheri-Behrouzi, Azadeh; Rauh, Manfred

    2013-04-01

    Disorders of thyroid function have been inconsistently described in cystic fibrosis (CF) patients and in CF transmembrane regulator protein knockout animals. The literature lacks reports on iodine status of CF individuals. We hypothesize, that iodine deficiency is common in CF and account for abnormal thyroid function in CF patients. We investigated 129 children, adolescents, and adults with CF, who were living in the northern part of Bavaria/Germany. Malnutrition and lung function were analyzed. Urinary iodine excretion, TSH (thyroid-stimulating hormone), and ft4 (free thyroxine) were measured and set in relation to population-based, age-adjusted reference ranges. Subclinical hypothyroidism (normal fT4, elevated TSH) was found in 11.6% of subjects, and iodine deficiency in 83.7%. No correlations were found with age, BMI, status of malnutrition, or lung function. Dramatic iodine deficiency was found in our cohort of CF patients. This condition can cause subclinical hypothyroidism; therefore, an individual iodine supplementation program is necessary and should be started immediately. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

  13. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes

    OpenAIRE

    Tran, Thai Q.; Ishak Gabra, Mari B.; Lowman, Xazmin H.; Yang, Ying; Reid, Michael A.; Pan, Min; O’Connor, Timothy R.; Kong, Mei

    2017-01-01

    Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damag...

  14. Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.

    Science.gov (United States)

    Romero-Moya, Damià; Santos-Ocaña, Carlos; Castaño, Julio; Garrabou, Gloria; Rodríguez-Gómez, José A; Ruiz-Bonilla, Vanesa; Bueno, Clara; González-Rodríguez, Patricia; Giorgetti, Alessandra; Perdiguero, Eusebio; Prieto, Cristina; Moren-Nuñez, Constanza; Fernández-Ayala, Daniel J; Victoria Cascajo, Maria; Velasco, Iván; Canals, Josep Maria; Montero, Raquel; Yubero, Delia; Jou, Cristina; López-Barneo, José; Cardellach, Francesc; Muñoz-Cánoves, Pura; Artuch, Rafael; Navas, Plácido; Menendez, Pablo

    2017-07-01

    Coenzyme Q 10 (CoQ 10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ 10 biosynthesis (COQ genes) cause primary CoQ 10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ 10 ], CoQ 10 biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4 ed -iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4 ed -iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ 10 deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ 10 deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation. Stem Cells 2017;35:1687-1703. © 2017 AlphaMed Press.

  15. Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma.

    Directory of Open Access Journals (Sweden)

    Tim F Cloughesy

    2008-01-01

    Full Text Available There is much discussion in the cancer drug development community about how to incorporate molecular tools into early-stage clinical trials to assess target modulation, measure anti-tumor activity, and enrich the clinical trial population for patients who are more likely to benefit. Small, molecularly focused clinical studies offer the promise of the early definition of optimal biologic dose and patient population.Based on preclinical evidence that phosphatase and tensin homolog deleted on Chromosome 10 (PTEN loss sensitizes tumors to the inhibition of mammalian target of rapamycin (mTOR, we conducted a proof-of-concept Phase I neoadjuvant trial of rapamycin in patients with recurrent glioblastoma, whose tumors lacked expression of the tumor suppressor PTEN. We aimed to assess the safety profile of daily rapamycin in patients with glioma, define the dose of rapamycin required for mTOR inhibition in tumor tissue, and evaluate the antiproliferative activity of rapamycin in PTEN-deficient glioblastoma. Although intratumoral rapamycin concentrations that were sufficient to inhibit mTOR in vitro were achieved in all patients, the magnitude of mTOR inhibition in tumor cells (measured by reduced ribosomal S6 protein phosphorylation varied substantially. Tumor cell proliferation (measured by Ki-67 staining was dramatically reduced in seven of 14 patients after 1 wk of rapamycin treatment and was associated with the magnitude of mTOR inhibition (p = 0.0047, Fisher exact test but not the intratumoral rapamycin concentration. Tumor cells harvested from the Ki-67 nonresponders retained sensitivity to rapamycin ex vivo, indicating that clinical resistance to biochemical mTOR inhibition was not cell-intrinsic. Rapamycin treatment led to Akt activation in seven patients, presumably due to loss of negative feedback, and this activation was associated with shorter time-to-progression during post-surgical maintenance rapamycin therapy (p < 0.05, Logrank test

  16. PKU patients on a relaxed diet may be at risk for micronutrient deficiencies.

    Science.gov (United States)

    Rohde, C; von Teeffelen-Heithoff, A; Thiele, A G; Arelin, M; Mütze, U; Kiener, C; Gerloff, J; Baerwald, C; Schultz, S; Heller, C; Müller, A S; Kiess, W; Beblo, S

    2014-01-01

    To investigate micronutrient supply in phenylketonuria (PKU) patients on a relaxed diet. Sixty-seven patients (6-45 years) with a phenylalanine tolerance ≥ 600 mg/day were included in the study. From a 3-day diet record, protein supply as well as consumption of essential amino acids and several micronutrients were assessed and compared with the current recommendations and data for the healthy population. Protein supply and consumption of all essential amino acids were sufficient in all patients. Supply of micronutrients depended on dietary regime. Patients with a total protein supply of 120% or more of the recommended amount and at least 0.5 g protein per kg body weight from amino-acid mixture (AAM) were sufficiently supplied with all investigated micronutrients. All patients without AAM supplement showed severe micronutrient deficiencies in their diet records. PKU patients under a relaxed diet are at risk of an insufficient nutrient supply, if they have first no substitution with AAM, second a protein supply less than 0.5 g per kg body weight from AAM or third a total protein supply less than 120% of the recommendations. Therefore, close monitoring, specific dietary counseling and potential supplementation is mandatory to prevent micronutrient deficiencies in PKU patients.

  17. Strains Responsible for Invasive Meningococcal Disease in Patients With Terminal Complement Pathway Deficiencies.

    Science.gov (United States)

    Rosain, Jérémie; Hong, Eva; Fieschi, Claire; Martins, Paula Vieira; El Sissy, Carine; Deghmane, Ala-Eddine; Ouachée, Marie; Thomas, Caroline; Launay, David; de Pontual, Loïc; Suarez, Felipe; Moshous, Despina; Picard, Capucine; Taha, Muhamed-Kheir; Frémeaux-Bacchi, Véronique

    2017-04-15

    Patients with terminal complement pathway deficiency (TPD) are susceptible to recurrent invasive meningococcal disease (IMD). Neisseria meningitidis (Nm) strains infecting these patients are poorly documented in the literature. We identified patients with TPD and available Nm strains isolated during IMD. We investigated the genetic basis of the different TPDs and the characteristics of the Nm strains. We included 56 patients with C5 (n = 8), C6 (n = 20), C7 (n = 18), C8 (n = 9), or C9 (n = 1) deficiency. Genetic study was performed in 47 patients and 30 pathogenic variants were identified in the genes coding for C5 (n = 4), C6 (n = 5), C7 (n = 12), C8 (n = 7), and C9 (n = 2). We characterized 61 Nm strains responsible for IMD in the 56 patients with TPD. The most frequent strains belonged to groups Y (n = 27 [44%]), B (n = 18 [30%]), and W (n = 8 [13%]). Hyperinvasive clonal complexes (CC11, CC32, CC41/44, and CC269) were responsible for 21% of IMD cases. The CC23 predominates and represented 26% of all invasive isolates. Eleven of the 15 clonal complexes identified fit to 12 different clonal complexes belonging to carriage strains. Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD. © The Author 217. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  18. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency.

    Science.gov (United States)

    El Euch-Fayache, Ghada; Bouhlal, Yosr; Amouri, Rim; Feki, Moncef; Hentati, Fayçal

    2014-02-01

    Ataxia with vitamin E deficiency is an autosomal recessive cerebellar ataxia caused by mutations in the α-tocopherol transfer protein coding gene localized on chromosome 8q, leading to lower levels of serum vitamin E. More than 91 patients diagnosed with ataxia with vitamin E deficiency have been reported worldwide. The majority of cases originated in the Mediterranean region, and the 744delA was the most common mutation among the 22 mutants previously described. We examined the clinical and molecular features of a large cohort of 132 Tunisian patients affected with ataxia with vitamin E deficiency. Of these patients, nerve conduction studies were performed on 45, and nerve biopsy was performed on 13. Serum vitamin E was dramatically reduced for 105 of the patients analysed. Molecular analysis revealed that 91.7% of the patients (n = 121) were homozygous for the 744delA mutation. Three other mutations were detected among the remaining patients (8.3%, n = 11) in the homozygous state. Two were previously reported (400C>T and 205-1G>T), and one was novel (553+1T>A). Age of onset was 13.2 ± 5.9 years, with extremes of 2 and 37 years. All described patients exhibited persistent progressive cerebellar ataxia with generally absent tendon reflexes. Deep sensory disturbances, pyramidal syndrome and skeletal deformities were frequent. Head tremor was present in 40% of the patients. Absence of neuropathy or mild peripheral neuropathy was noted in more than half of the cohort. This is the largest study of the genetic, clinical and peripheral neuropathic characteristics in patients with ataxia and vitamin E deficiency. The 744delA mutation represents the most common pathological mutation in Tunisia and worldwide, likely because of a Mediterranean founder effect. Our study led us to suggest that any patient displaying an autosomal recessive cerebellar ataxia phenotype with absent tendon reflexes and minor nerve abnormalities should first be screened for the 744delA mutation

  19. Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms

    Directory of Open Access Journals (Sweden)

    Cheillan David

    2012-12-01

    Full Text Available Abstract A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD. Urine guanidinoacetate (GAA and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.1.1.2] and 10 X-linked creatine transporter (SLC6A8 but no AGAT (GATM [L-arginine/glycine amidinotransferase (EC 2.1.4.1] deficient patients were identified in this manner. Three additional affected sibs were further identified after familial inquiry (1 brother with GAMT deficiency and 2 brothers with SLC6A8 deficiency in two different families. The prevalence of PCD in this population was 0.25% (0.09% and 0.16% for GAMT and SLC6A8 deficiencies, respectively. Seven new PCD-causing mutations were discovered (2 nonsense [c.577C > T and c.289C > T] and 1 splicing [c.391 + 15G > T] mutations for the GAMT gene and, 2 missense [c.1208C > A and c.926C > A], 1 frameshift [c.930delG] and 1 splicing [c.1393-1G > A] mutations for the SLC6A8 gene. No hot spot mutations were observed in these genes, as all the mutations were distributed throughout the entire gene sequences and were essentially patient/family specific. Approximately one fifth of the mutations of SLC6A8, but not GAMT, were attributed to neo-mutation, germinal or somatic mosaicism events. The only SLC6A8-deficient female patient in our series presented with the severe phenotype usually characterizing affected male patients, an observation in agreement with recent evidence that is in support of the fact that this X-linked disorder might be more frequent than expected in the female population with intellectual disability.

  20. Cobalamin deficiency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital.

    Science.gov (United States)

    Couderc, A-L; Camalet, J; Schneider, S; Turpin, J M; Bereder, I; Boulahssass, R; Gonfrier, S; Bayer, P; Guerin, O; Brocker, P

    2015-02-01

    Cobalamin deficiency is frequent in elderly patients and the main aetiologies are food-cobalamin malabsorption and pernicious anaemia. The aim of our retrospective study was to identify the causes and methods of management of cobalamin deficiency at Nice geriatric university hospital. A retrospective monocentric study was conducted over 14 months at Nice geriatric hospital, which included patients with cobalamin deficiency having received supplementation. The clinical and paraclinical data, etiological diagnosis, treatment and follow-up modalities were analyzed retrospectively. We studied 125 elderly patients whose median age was 85.5 ± 7 years. The etiological diagnosis was food-cobalamin malabsorption for 72 patients (57.6 %), nutritional cobalamin deficiency for 15 patients (12 %), pernicious anaemia for 12 patients (9.6 %) and there was no etiological diagnosis for 26 patients (20.8 %). Concerning cobalamin therapy, 111 patients (88.8 %) received oral therapy and 14 (11.2 %) intramuscular therapy. Vitamin B12 levels increased significantly after supplementation (ppatients with dementia (p=0.04) and food-cobalamin malabsorption. Our study showed the importance of food-cobalamin malabsorption in etiological diagnosis in accordance with the literature, but also the non-negligible share of nutritional cobalamin deficiency. Mainly oral cobalamin supplementation was used in our study with a significant increase in vitamin B12 levels. An oral cobalamin regimen is proposed for elderly patients with cobalamin deficiency but with no severe neurological signs.

  1. Ponatinib promotes a G1 cell-cycle arrest of merlin/NF2-deficient human schwann cells.

    Science.gov (United States)

    Petrilli, Alejandra M; Garcia, Jeanine; Bott, Marga; Klingeman Plati, Stephani; Dinh, Christine T; Bracho, Olena R; Yan, Denise; Zou, Bing; Mittal, Rahul; Telischi, Fred F; Liu, Xue-Zhong; Chang, Long-Sheng; Welling, D Bradley; Copik, Alicja J; Fernández-Valle, Cristina

    2017-05-09

    Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/β, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/β, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation.

  2. The prevalence of iron deficiency anaemia in patients undergoing bariatric surgery.

    Science.gov (United States)

    Khanbhai, M; Dubb, S; Patel, K; Ahmed, A; Richards, T

    2015-01-01

    As bariatric surgery rates continue to climb, anaemia will become an increasing concern. We assessed the prevalence of anaemia and length of hospital stay in patients undergoing bariatric surgery. Prospective data (anaemia [haemoglobin bariatric surgery. Results from a prospective database of 1530 patients undergoing elective general surgery were used as a baseline. Fifty-seven patients (14%) were anaemic pre-operatively, of which 98% were females. Median MCV (fL) and overall median ferritin (μg/L) was lower in anaemic patients (83 vs. 86, p=0.001) and (28 vs. 61, psurgery patients, prevalence of anaemia was similar (14% vs. 16%) but absolute iron deficiency was more common in those undergoing bariatric surgery; microcytosis pbariatric surgery. In bariatric patients with anaemia there was an overall increased length of hospital stay. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  3. Low-frequency electrotherapy for female patients with detrusor underactivity due to neuromuscular deficiency.

    Science.gov (United States)

    Xu, Dan-Feng; Zhang, Shen; Wang, Cun-Zhou; Li, Jun; Qu, Chuang-Yu; Cui, Xin-Gang; Zhao, Sheng-Jia

    2012-08-01

    The aim of the study was to assess the efficacy of low-frequency electrotherapy (LFE) for female patients with early-stage detrusor underactivity (DUA) due to neuromuscular deficiency. A total of 102 female patients were divided randomly into four groups: LFE-NC (normal compliance), LFE-LC (low compliance), CON (control)-NC and CON-LC. Patients in the LFE-NC and LFE-LC groups received LFE, and those in the CON-NC and CON-LC groups received conservative treatment. Urodynamic evaluation was performed before and after treatment. After treatment, 82 % of the LFE-NC regained detrusor contractility, whereas only 2 (8 %) of the CON-NC had normal detrusor contraction. None of LFE-LC or CON-LC regained detrusor contractility (p 0.05). LFE was more effective for DUA patients with normal compliance; these patients benefited from LFE, but DUA patients with low compliance did not.

  4. Purine biosynthesis in Chinese Hamster cell mutants and human fibroblasts partially deficient in adenylosuccinate lyase

    International Nuclear Information System (INIS)

    Laikind, P.K.; Gruber, H.E.; Hoffer, M.; Jansen, I.; Miller, L.; Seegmiller, J.E.

    1986-01-01

    In a study of purine nucleotide metabolism of CHO-Ade I cells and fibroblasts from an adenylocsuccinate (AS) and SAICA riboside over-producing pattient the authors examined the effect of ASMP lyase deficiency on brachpoint enzyme activities and on de novo synthesis by comparison to the control cell lines, wild type parent cells (CHO-K1) and fibroblasts from age-matched normal individuals, respectively. The rate of newly-formed purine synthesis and excretion was measured by determining the amount of C 14-formate incorporatted into adenine, hypoxanthine, and guanasine moities. The nucleotide, nucleoside and base content of cells and media were analyzed by hhigh-pressure liquid chrromatography. Results are presented

  5. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil.

    Science.gov (United States)

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; Souza, Altay Alves Lino de; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of sangue seco por meio de nefelometria. Aqueles em que a concentração de AAT no sangue seco foi ≤ 2,64 mg/dl foram submetidos a dosagem sérica de AAT. Aqueles em que a concentração sérica de AAT foi sangue seco ≤ 2,64 mg/dl, e 24 (2,6% da amostra) apresentaram concentração sérica de AAT < 113 mg/dl. A distribuição genotípica nesse subgrupo de 24 pacientes foi a seguinte: PI*MS, em 3 (12,5%); PI*MZ, em 13 (54,2%); PI*SZ, em 1 (4,2%); PI*SS, em 1 (4,2%); e PI*ZZ, em 6 (25,0%). Na amostra estudada, a prevalência global da deficiência de AAT foi de 2,8% e a prevalência do genótipo PI*ZZ (deficiência grave de AAT) foi de 0,8%. A prevalência da deficiência de AAT em pacientes com DPOC no Brasil é semelhante àquela encontrada na maioria dos países e reforça a recomendação de que se deve medir a concentração de AAT em todos pacientes com DPOC.

  6. Effects of IKAP/hELP1 deficiency on gene expression in differentiating neuroblastoma cells: implications for familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Rachel Cohen-Kupiec

    Full Text Available Familial dysautonomia (FD is a developmental neuropathy of the sensory and autonomous nervous systems. The IKBKAP gene, encoding the IKAP/hELP1 subunit of the RNA polymerase II Elongator complex is mutated in FD patients, leading to a tissue-specific mis-splicing of the gene and to the absence of the protein in neuronal tissues. To elucidate the function of IKAP/hELP1 in the development of neuronal cells, we have downregulated IKBKAP expression in SHSY5Y cells, a neuroblastoma cell line of a neural crest origin. We have previously shown that these cells exhibit abnormal cell adhesion when allowed to differentiate under defined culture conditions on laminin substratum. Here, we report results of a microarray expression analysis of IKAP/hELP1 downregulated cells that were grown on laminin under differentiation or non-differentiation growth conditions. It is shown that under non-differentiation growth conditions, IKAP/hELP1 downregulation affects genes important for early developmental stages of the nervous system, including cell signaling, cell adhesion and neural crest migration. IKAP/hELP1 downregulation during differentiation affects the expression of genes that play a role in late neuronal development, in axonal projection and synapse formation and function. We also show that IKAP/hELP1 deficiency affects the expression of genes involved in calcium metabolism before and after differentiation of the neuroblastoma cells. Hence, our data support IKAP/hELP1 importance in the development and function of neuronal cells and contribute to the understanding of the FD phenotype.

  7. Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients.

    Science.gov (United States)

    Annibale, B; Severi, C; Chistolini, A; Antonelli, G; Lahner, E; Marcheggiano, A; Iannoni, C; Monarca, B; Delle Fave, G

    2001-01-01

    Iron deficiency anemia has been reported as the most frequent extraintestinal symptom in adult celiac disease. Prospective studies on the effect of gluten-free diet on recovery from iron deficiency anemia are lacking. The aim of this study was to verify in adult patients with celiac disease the efficacy of and the time course of recovery from iron deficiency anemia by a gluten-free diet alone. We studied 190 consecutive adult patients with iron deficiency anemia, screened for celiac disease by duodenal biopsies. New diagnosed celiac patients were invited to follow a gluten-free diet alone without iron supplementation. After 6 months of diet, duodenal biopsies were performed and hematological tests were repeated at 6, 12, and 24 months. Celiac disease was diagnosed in 26 (24 women, 2 men; 13.7%) adult patients. After 6 months of gluten-free diet 14 of 18 (77.8%) female patients recovered from anemia, but only 5 of 18 (27.8%) reversed from iron deficiency. At 12-month control all but one patient (94.4%) recovered from anemia and 9 patients (50%) from iron deficiency. After 24 months of diet, only the patient who did not recover from anemia at 12-month control was still anemic, whereas 10 patients (55.5%) reversed from iron deficiency. A significant inverse correlation (r = -0.7141, p = 0.0003) between increase of Hb concentrations and decrease of individual histological scores of duodenitis was observed. A screening for celiac disease should be carried out in adult patients with iron deficiency anemia. Recovery from anemia occurs between 6 and 12 months on a gluten-free diet alone as a consequence of normalization of histological alterations of the intestinal mucosa.

  8. The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

    Science.gov (United States)

    Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

    2000-05-25

    DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

  9. Etoposide (VP-16) sensitizes p53-deficient human non-small cell lung cancer cells to caspase-7-mediated apoptosis.

    Science.gov (United States)

    Chiu, C-C; Lin, C-H M Y; Fang, K

    2005-05-01

    Human non-small-cell-lung-cancer (NSCLC) cells of (p)53-null genotype were exposed to low-dosage topoisomearse II inhibitor etoposide (VP-16). The cellular proliferation rate could be effectively inhibited by VP-16 in dose-dependent manner. The effective drug concentration for growth inhibition could be as low as 0.5 microM and the apoptotic phenotype became evident 48 h later. In H1299 cells, VP-16-induced cytotoxic effect was demonstrated associated with apoptosis that disappeared when restored with wild-type p53. Cell cycle analysis revealed that, upon VP-16 induction, cell death began with growth arrest by accumulating cells at the G(2)-M phase. The cells at sub-G(1) phase increased at the expense of those at G(2)-M transition state. To assess the regulation of cell cycle modulators, western blot analysis of H1299 cell lysates showed the release of apoptosis initiator, cytochrome c and apaf-1 hours following drug induction. The cleavage of downstream effectors, procaspase-9 and procaspase-7, but not procaspase-3, was accompanied with proteolysis of poly-(ADP-ribose) polymerase (PARP). VP-16-activated procaspase-7 cleavage was abrogated in cells with ectopically expressed p53. On the other hand, the inhibited procaspase-7 fragmentation by caspase-specific inhibitor reversed apoptotic phenotype caused by drug induction. Thus, VP-16-induced apoptotic cell death was contributed by caspase-7 activation in(p)53-deficient human NSCLC cells.

  10. Deficient Fas expression by CD4+ CCR5+ T cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Julià, Eva; Montalban, Xavier; Al-Zayat, Hammad

    2006-01-01

    OBJECTIVE: To evaluate whether T cells expressing CCR5 and CXCR3 from multiple sclerosis (MS) patients are more resistant to apoptosis. METHODS: Expression of CD69, TNF-R1, Fas, FasL, bcl-2, and bax was investigated in 41 MS patients and 12 healthy controls by flow cytometry in CD4+ and CD8+ T...... cells expressing CCR5 and CXCR3. RESULTS: In MS patients, the percentage of CD69 was increased and Fas expression decreased in CD4+ CCR5+ T cells. INTERPRETATION: The lower Fas expression in activated CD4+ CCR5+ T cells might contribute to disease pathogenesis by prolonging cell survival and favoring...

  11. Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Sérgio M Pinto

    Full Text Available The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole-sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency.

  12. Intracellular vesicles as reproduction elements in cell wall-deficient L-form bacteria.

    Directory of Open Access Journals (Sweden)

    Yves Briers

    Full Text Available Cell wall-deficient bacteria, or L-forms, represent an extreme example of bacterial plasticity. Stable L-forms can multiply and propagate indefinitely in the absence of a cell wall. Data presented here are consistent with the model that intracellular vesicles in Listeria monocytogenes L-form cells represent the actual viable reproductive elements. First, small intracellular vesicles are formed along the mother cell cytoplasmic membrane, originating from local phospholipid accumulation. During growth, daughter vesicles incorporate a small volume of the cellular cytoplasm, and accumulate within volume-expanding mother cells. Confocal Raman microspectroscopy demonstrated the presence of nucleic acids and proteins in all intracellular vesicles, but only a fraction of which reveals metabolic activity. Following collapse of the mother cell and release of the daughter vesicles, they can establish their own membrane potential required for respiratory and metabolic processes. Premature depolarization of the surrounding membrane promotes activation of daughter cell metabolism prior to release. Based on genome resequencing of L-forms and comparison to the parental strain, we found no evidence for predisposing mutations that might be required for L-form transition. Further investigations revealed that propagation by intracellular budding not only occurs in Listeria species, but also in L-form cells generated from different Enterococcus species. From a more general viewpoint, this type of multiplication mechanism seems reminiscent of the physicochemical self-reproducing properties of abiotic lipid vesicles used to study the primordial reproduction pathways of putative prokaryotic precursor cells.

  13. Cryptococcal meningitis and cerebral toxoplasmosis in a patient with acquired immune deficiency syndrome.

    Science.gov (United States)

    Bahls, F; Sumi, S M

    1986-01-01

    A 34-year-old homosexual male developed cryptococcal meningitis as the initial manifestation of Acquired Immune Deficiency Syndrome (AIDS). With antifungal therapy he improved. Six weeks later he developed focal motor seizures and progressive hemiplegia. Computer assisted tomography revealed multiple, ring-enhancing, low density lesions. The patient expired and at necropsy he was found to have multiple toxoplasma brain abscesses as well as chronic cryptococcal meningitis. This case demonstrates that in a patient with AIDS with pre-existing central nervous system infection who develops new neurological symptoms the possibility of a second and potentially treatable infection must be considered and its diagnosis pursued vigorously. Images PMID:3958746

  14. Correction of transverse maxillary deficiency and anterior open bite in an adult Class III skeletal patient

    Directory of Open Access Journals (Sweden)

    Prerna Hoogan Teja

    2016-01-01

    Full Text Available Transverse maxillary deficiency may be associated with sagittal or vertical problems of the maxilla or mandible. It may contribute to unilateral or bilateral posterior crossbite, anterior dental crowding, and unesthetic black buccal corridors on smiling. An adequate transverse dimension is important for stable and proper functional occlusion. Surgically, assisted rapid palatal expansion has been the treatment of choice to resolve posterior crossbite in skeletally mature patients. The following case report presents an adult Class III skeletal patient with an anterior open bite and bilateral posterior crossbite which was treated by surgically assisted rapid maxillary expansion with satisfactory outcomes.

  15. Anaesthesia management in a patient with a severe biotinidase deficiency for congenital scoliosis repair

    Directory of Open Access Journals (Sweden)

    Ebrahim Almasri

    2016-01-01

    Full Text Available A 17 year old female patient with a biotinidase enzyme deficiency, cerebral palsy, aphamis, generalized hyperreflexia and spasticity, epilepsy and mental retardation came for the severe kyphoscoliotic deformity correction. Biotinidase enzyme deficiency is an autosomal recessive disorder with incidence of 1:60,000 neonatal birth. Treatment with biotin results in a rapid biochemical and clinical improvement. This enzyme deficiency involves neurological, neuromuscular, respiratory, dermatological and immunological problems. If untreated it can lead to convulsions, coma and death. Cobb’s angle that measures the curvature of scoliosis, determined by measurements made on X rays in this case was 120° with clinical presentation of recurrent respiratory tract infection, inability to maintain sagittal posture, inability to eat or feed and difficulty in nursing care. Anaesthetic management in these patients should focus primarily on associated comorbidities and congenital anomalies affecting the course of the perioperative management and thereafter comprehensive preoperative strategies must be executed to enhance the safety profile during the surgery.

  16. Comparison of vitamin D deficiency and magnitude of severity of vitamin D deficiency in cirrhotic and non-cirrhotic patients with chronic hepatitis C in a tertiary care hospital Rawalpindi, Pakistan

    International Nuclear Information System (INIS)

    Hamid, S.; Faheem, M.; Ambreen, S.; Tirmizi, A.; Umar, M.

    2017-01-01

    Objective: To determine Vitamin D deficiency in both cirrhotic and non-cirrhotic patients with chronic hepatitis C (CHC). Methodology: We conducted a cross-sectional study at Centre for Liver and Digestive Diseases (CLD), Holy Family Hospital, Rawalpindi, Pakistan from August 2015 to February 2016 and included 120 Patients with CHC with or without cirrhosis. Two groups were formed and vitamin D levels were measured and level of severity was assessed. Results: Out of 120 patients, 94(78.3%) patients had Vitamin D deficiency. 63(100%) cirrhotic patients and 31 54.4%) non cirrhotic patients had Vitamin D deficiency. In cirrhotic patients, 26(41.3%) had mild and 36(58.7%) had moderate Vitamin D deficiency while in non-cirrhotic patients 25(43.9%) had mild and 6(10.5%) had moderate deficiency. No patient with severe Vitamin D deficiency was observed. Conclusion: Most of the patients infected with CHC suffer from vitamin D deficiency. This was observed more in cirrhotic patients than non-cirrhotic patients. Moreover, positive correlation was observed among vitamin D deficiency and stage of fibrosis. (author)

  17. Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening.

    Science.gov (United States)

    Arias, Angela; Corbella, Marc; Fons, Carmen; Sempere, Angela; García-Villoria, Judit; Ormazabal, Aida; Poo, Pilar; Pineda, Mercé; Vilaseca, María Antonia; Campistol, Jaume; Briones, Paz; Pàmpols, Teresa; Salomons, Gajja S; Ribes, Antonia; Artuch, Rafael

    2007-11-01

    To report the prevalence of creatine transporter deficiency in males with mental retardation and to study whether a protein-rich food intake might be a potential diagnostic pitfall. We determined creatine/creatinine ratio in urine samples from 1600 unrelated male patients with mental retardation and/or autism. Urine creatine was analyzed by HPLC-MS/MS. Thirty-three of 1600 cases showed increased urine creatine/creatinine ratio. Four out of these thirty-three cases were definitively diagnosed with creatine transporter deficiency, while the other 29 were false positive results. Significantly higher values were observed for urine Cr/Crn ratio in healthy volunteers after a meal based on beef or oily fish as compared to eggs, pasta or salad (Wilcoxon test: pdeficiency, and they may be due to intake of meals rich in creatine prior to urine samples analysis.

  18. Recurrent Intestinal Obstruction in a Patient with Selective IgA Deficiency.

    Science.gov (United States)

    Hui, Chee-Kin

    2016-11-01

    A 32 year old woman presented with acute onset of abdominal pain and fever. An urgent computerised tomography (CT) of the whole abdomen showed dilated loop at the terminal ileum in the right lower abdomen with thickening of the wall and oedema. The CT was suggestive of distal small bowel obstruction at the ileum with surrounding wall oedema. Multiple biopsies taken from the terminal ileum and colon on colonoscopy were all unremarkable. She represented one-year later with a recurrence of intestinal obstruction. CT enteroclysis showed collapse at the distal 3 cm segment of the terminal ileum. There was no associated wall thickening, active inflammatory changes or ileitis. This was suspicious of post-inflammatory change or fibrosis. She was subsequently found to have selective IgA deficiency with recurrent infection in the terminal ileum resulting in intestinal obstruction. In conclusion, selective IgA deficiency should be considered in patients with recurrent intestinal obstruction without anatomical obstructions.

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  20. Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Seersholm, Niels; Perch, Michael

    2014-01-01

    : Compared with COPD without AATD, AATD patients are younger, more often males, have a lower prevalence of cardio-vascular diseases and diabetes mellitus, and higher prevalence of osteoporosis. Moreover, they have better prognosis, partly due to greater chance of receiving a lung transplantation....... on average about 17 years younger than patients without AATD. Cardio-vascular diseases and diabetes mellitus were significantly less prevalent among patients with AATD (60.4% versus 70.3% (P ...INTRODUCTION: Data on patients with alpha1-antitrypsine deficiency (AATD) on long-term oxygen therapy (LTOT) is sparse. The aim of this study was to present the incidence of patients with AATD on LTOT, and compare their characteristics, comorbidities and prognosis (lung transplantation, termination...

  1. Mast cell-deficient kit mice develop house dust mite-induced lung inflammation despite impaired eosinophil recruitment.

    Science.gov (United States)

    de Boer, J Daan; Yang, Jack; van den Boogaard, Florry E; Hoogendijk, Arie J; de Beer, Regina; van der Zee, Jaring S; Roelofs, Joris J T H; van 't Veer, Cornelis; de Vos, Alex F; van der Poll, Tom

    2014-01-01

    Mast cells are implicated in allergic and innate immune responses in asthma, although their role in models using an allergen relevant for human disease is incompletely understood. House dust mite (HDM) allergy is common in asthma patients. Our aim was to investigate the role of mast cells in HDM-induced allergic lung inflammation. Wild-type (Wt) and mast cell-deficient Kit(w-sh) mice on a C57BL/6 background were repetitively exposed to HDM via the airways. HDM challenge resulted in a rise in tryptase activity in bronchoalveolar lavage fluid (BALF) of Wt mice, indicative of mast cell activation. Kit(w-sh) mice showed a strongly attenuated HDM- induced recruitment of eosinophils in BALF and lung tissue, accompanied by reduced pulmonary levels of the eosinophil chemoattractant eotaxin. Remarkably, Kit(w-sh) mice demonstrated an unaltered capacity to develop lung pathology and increased mucus production in response to HDM. The increased plasma IgE in response to HDM in Wt mice was absent in Kit(w-sh) mice. These data contrast with previous reports on the role of mast cells in models using ovalbumin as allergen in that C57BL/6 Kit(w-sh) mice display a selective impairment of eosinophil recruitment without differences in other features of allergic inflammation. Copyright © 2013 S. Karger AG, Basel

  2. Increased prevalence of growth hormone deficiency in patients with vernal keratoconjuntivitis; an interesting new association.

    Science.gov (United States)

    Stagi, Stefano; Pucci, Neri; di Grande, Laura; de Libero, Cinzia; Caputo, Roberto; Pantano, Stefano; Seminara, Salvatore; de Martino, Maurizio; Novembre, Elio

    2014-01-01

    Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that mainly affects children living in temperate areas. The notable difference between genders and VKC's resolution with puberty have persistently suggested a role of hormonal factors in VKC development. To describe six cases of males with VKC and growth hormone deficiency (GHD) reported as a long-term follow-up during rhGH treatment. Six consecutive male patients (median age at GHD diagnosis 9.7, range 7.9 to 13.1 years) with VKC, were recruited from July 2005 to July 2013 at the Paediatric Endocrinology Unit of Anna Meyer Children's Hospital in Florence, Italy. In these patients, anthropometric data were collected periodically. In three of these patients, data were collected to near-adult or adult height. Familial history was uneventful for all patients. The target height was normal, ranging from 0.65 standard deviation scores (SDS) to 2.01 SDS. The patients showed a normal birth-weight (from -1.21 to 1.35 SDS) and birth-length (from -0.93 to 1.21 SDS). At GHD diagnosis, all of the patients exhibited demonstrated important growth retardation (from -2.05 to -2.78 SDS). Plasmatic concentrations of IGF-1 and IGFBP-3 were low (from -1.85 to -3 SDS and from -1.81 to -2.76 SDS, respectively). GH stimulation tests showed classic GHD symptoms in all of the patients. Pubertal onset was normal. All of the patients treated with rhGH responded well to rhGH treatment. Adult height, evaluated in three patients, was in accordance with their target height. To our current knowledge, we have described for the first time six patients affected by VKC with GH deficiency, in some of whom we performed a long-term follow-up to adult height. Further studies will be needed to establish whether GHD may be a common feature of VKC patients. Nevertheless, it appears to be useful to carefully follow statural growth of VKC patients, while the possibility of a GH deficiency must to be taken into account in the presence of growth

  3. [Advances in the research of zinc deficiency and zinc supplementation treatment in patients with severe burns].

    Science.gov (United States)

    Wang, X X; Zhang, M J; Li, X B

    2018-01-20

    Zinc is one of the essential trace elements in human body, which plays an important role in regulating acute inflammatory response, glucose metabolism, anti-oxidation, immune and gastrointestinal function of patients with severe burns. Patients with severe burns may suffer from zinc deficiency because of insufficient amount of zinc intake from the diet and a large amount of zinc lose through wounds and urine. Zinc deficiency may affect their wound healing process and prognosis. This article reviews the characteristics of zinc metabolism in patients with severe burns through dynamic monitoring the plasma and urinary concentration of zinc. An adequate dosage of zinc supplemented to patients with severe burns by an appropriate method can increase the level of zinc in plasma and skin tissue and improve wound healing, as well as reduce the infection rates and mortality. At the same time, it is important to observe the symptoms and signs of nausea, dizziness, leukopenia and arrhythmia in patients with severe burns after supplementing excessive zinc.

  4. Survival of endometrial cancer patients with lymphatic invasion and deficient mismatch repair expression.

    Science.gov (United States)

    Terada, Keith Y; Black, Michael; Terada, Laura H; Davis, James; Shimizu, David M

    2013-04-01

    This study examines patients under the age of 70 with endometrial cancer and lymphatic invasion or lymph node metastases. Survival of patients with loss of tumor mismatch repair expression is compared to survival of patients with normal mismatch repair expression. This is a retrospective review of patients treated from 1998-2009 for carcinoma of the endometrium. All patients with lymphatic invasion, including lymph node metastases, had immunohistochemical staining of the primary tumor for loss of expression of the mismatch repair genes MLH1, PMS2, MSH6, and MSH2. Overall survival and disease specific survival were compared using Kaplan-Meier plots. Sixty-six patients were identified for inclusion; 26 demonstrated loss of mismatch repair expression and 40 demonstrated normal mismatch repair expression. Overall survival and disease specific survival were significantly better in the group with defective mismatch repair expression. Subgroup analysis of FIGO stage 3C patients also showed significantly better survival in patients with deficient mismatch repair expression. For patients with endometrial cancer and lymphatic invasion, patients demonstrating loss of mismatch repair expression in the primary tumor appear to have a significantly better survival than patients with normal mismatch repair expression. Further investigation appears warranted to examine a possible role of mismatch repair expression as a prognostic marker for high risk patients with endometrial cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Ligase-deficient yeast cells exhibit defective DNA rejoining and enhanced gamma ray sensitivity

    International Nuclear Information System (INIS)

    Moore, C.W.

    1982-01-01

    Yeast cells deficient in DNA ligase were also deficient in their capacity to rejoin single-strand scissions in prelabeled nuclear DNA. After high-dose-rate gamma irradiation (10 and 25 krads), cdc9-9 mutant cells failed to rejoin single-strand scissions at the restrictive temperature of 37 0 C. In contrast, parental (CDC9) cells (incubated with mutant cells both during and after irradiation) exhibited rapid medium-independent DNA rejoining after 10 min of post-irradiation incubation and slower rates of rejoining after longer incubation. Parental cells were also more resistant than mutant cells to killing by gamma irradiation. Approximately 2.5 +- 0.07 and 5.7 +- 0.6 single-strand breaks per 10 8 daltons were detected in DNAs from either CDC9 or cdc9-9 cells converted to spheroplasts immediately after 10 and 25 krads of irradiation, respectively. At the permissive temperature of 23 0 C, the cdc9-9 cells contained 2 to 3 times the number of DNA single-strand breaks as parental cells after 10 min to 4 h of incubation after 10 krads of irradiation, and two- to eightfold more breaks after 10 min to 2.5 h of incubation after 25 krads of irradiation. Rejoining of single-strand scissions was faster in medium. After only 10 min in buffered growth medium after 10 krads of irradiation, the number of DNA single-strand breaks was reduced to 0.32 +- 0.3 (at 23 0 C) or 0.21 +- 0.05 (at 37 0 C) per 10 8 daltons in parental cells, but remained at 2.1 +- 0.06 (at 23 0 C) or 2.3 +- 0.07 (at 37 0 C) per 10 8 daltons in mutant cells. After 10 or 25 krads of irradiation plus 1 h of incubation in medium at 37 0 C, only DNA from CDC9 cells was rejoined to the size of DNA from unirradiated cells, whereas at 23 0 C, DNAs in both strains were completely rejoined

  6. Preorchiectomy Leydig Cell Dysfunction in Patients With Testicular Cancer

    DEFF Research Database (Denmark)

    Bandak, Mikkel; Jørgensen, Niels; Juul, Anders

    2017-01-01

    /LH and cFT/LH from the controls. Logistic regression analysis with an abnormal cFT/LH ratio as outcome and clinical stage, tumor size, age, histology, presence of contralateral germ cell neoplasia in situ (GCNIS), and bilateral tumors as covariates was performed. RESULTS: In patients who were negative....... Increasing tumor size, contralateral GCNIS, and increasing age were associated with Leydig cell dysfunction. In patients positive for hCG (n = 187), all reproductive hormones except SHBG were different from controls (P cell dysfunction...... before orchiectomy. Contralateral GCNIS, increasing age, and increasing tumor size are associated with Leydig cell dysfunction. We hypothesize that patients with preexisting Leydig cell dysfunction are at increased risk of testosterone deficiency following treatment....

  7. Deficiency in DNA damage response of enterocytes accelerates intestinal stem cell aging inDrosophila.

    Science.gov (United States)

    Park, Joung-Sun; Jeon, Ho-Jun; Pyo, Jung-Hoon; Kim, Young-Shin; Yoo, Mi-Ae

    2018-03-07

    Stem cell dysfunction is closely linked to tissue and organismal aging and age-related diseases, and heavily influenced by the niche cells' environment. The DNA damage response (DDR) is a key pathway for tissue degeneration and organismal aging; however, the precise protective role of DDR in stem cell/niche aging is unclear. The Drosophila midgut is an excellent model to study the biology of stem cell/niche aging because of its easy genetic manipulation and its short lifespan. Here, we showed that deficiency of DDR in Drosophila enterocytes (ECs) accelerates intestinal stem cell (ISC) aging. We generated flies with knockdown of Mre11 , Rad50 , Nbs1 , ATM , ATR , Chk1 , and Chk2 , which decrease the DDR system in ECs. EC-specific DDR depletion induced EC death, accelerated the aging of ISCs, as evidenced by ISC hyperproliferation, DNA damage accumulation, and increased centrosome amplification, and affected the adult fly's survival. Our data indicated a distinct effect of DDR depletion in stem or niche cells on tissue-resident stem cell proliferation. Our findings provide evidence of the essential role of DDR in protecting EC against ISC aging, thus providing a better understanding of the molecular mechanisms of stem cell/niche aging.

  8. IMPACT OF VITAMIN D AND CALCIUM DEFICIENCY IN THE BONES OF PATIENTS UNDERGOING BARIATRIC SURGERY: A SYSTEMATIC REVIEW

    OpenAIRE

    CABRAL, Jefry Alberto Vargas; de SOUZA, Gabriela Pereira; NASCIMENTO, Juliana de Almeida; SIMONETI, Luis Fernando; MARCHESE, Carolina; SALES-PERES, Silvia Helena de Carvalho

    2016-01-01

    ABSTRACT Introduction: Bariatric surgery is considered the most effective tool in the control and treatment of severe obesity, but patients undergoing this procedure are at increased risk of developing nutritional deficiencies by limiting the intake and absorption of many nutrients. Objective: To assess the impact of vitamin D deficiency and calcium in bone in patients after gastric bypass in Roux-en-Y, pointing directly at the type of administration, doses and effects after surgery. Metho...

  9. Acupuncture Improves Intestinal Absorption of Iron in Iron-deficient Obese Patients: A Randomized Controlled Preliminary Trial

    OpenAIRE

    Xin-Cai Xie; Yan-Qiang Cao; Qian Gao; Chen Wang; Man Li; Shou-Gang Wei

    2017-01-01

    Background: Obesity has an adverse effect on iron status. Hepcidin-mediated inhibition of iron absorption in the duodenum is a potential mechanism. Iron-deficient obese patients have diminished response to oral iron therapy. This study was designed to assess whether acupuncture could promote the efficacy of oral iron supplementation for the treatment of obesity-related iron deficiency (ID). Methods: Sixty ID or ID anemia (IDA) patients with obesity were screened at Beijing Hospital of Traditi...

  10. PKC-epsilon deficiency alters progenitor cell populations in favor of megakaryopoiesis.

    Directory of Open Access Journals (Sweden)

    John C Kostyak

    Full Text Available It has long been postulated that Protein Kinase C (PKC is an important regulator of megakaryopoiesis. Recent contributions to the literature have outlined the functions of several individual PKC isoforms with regard to megakaryocyte differentiation and platelet production. However, the exact role of PKCε remains elusive.To delineate the role of PKCε in megakaryopoiesis.We used a PKCε knockout mouse model to examine the effect of PKCε deficiency on platelet mass, megakaryocyte mass, and bone marrow progenitor cell distribution. We also investigated platelet recovery in PKCε null mice and TPO-mediated signaling in PKCε null megakaryocytes. PKCε null mice have higher platelet counts due to increased platelet production compared to WT littermate controls (p<0.05, n = 8. Furthermore, PKCε null mice have more bone marrow megakaryocyte progenitor cells than WT littermate control mice. Additionally, thrombopoietin-mediated signaling is perturbed in PKCε null mice as Akt and ERK1/2 phosphorylation are enhanced in PKCε null megakaryocytes stimulated with thrombopoietin. Finally, in response to immune-induced thrombocytopenia, PKCε null mice recovered faster and had higher rebound thrombocytosis than WT littermate control mice.Enhanced platelet recovery could be due to an increase in megakaryocyte progenitor cells found in PKCε null mice as well as enhanced thrombopoietin-mediated signaling observed in PKCε deficient megakaryocytes. These data suggest that PKCε is a negative regulator of megakaryopoiesis.

  11. β1-Adrenergic receptor deficiency in ghrelin-expressing cells causes hypoglycemia in susceptible individuals.

    Science.gov (United States)

    Mani, Bharath K; Osborne-Lawrence, Sherri; Vijayaraghavan, Prasanna; Hepler, Chelsea; Zigman, Jeffrey M

    2016-09-01

    Ghrelin is an orexigenic gastric peptide hormone secreted when caloric intake is limited. Ghrelin also regulates blood glucose, as emphasized by the hypoglycemia that is induced by caloric restriction in mouse models of deficient ghrelin signaling. Here, we hypothesized that activation of β1-adrenergic receptors (β1ARs) localized to ghrelin cells is required for caloric restriction-associated ghrelin release and the ensuing protective glucoregulatory response. In mice lacking the β1AR specifically in ghrelin-expressing cells, ghrelin secretion was markedly blunted, resulting in profound hypoglycemia and prevalent mortality upon severe caloric restriction. Replacement of ghrelin blocked the effects of caloric restriction in β1AR-deficient mice. We also determined that treating calorically restricted juvenile WT mice with beta blockers led to reduced plasma ghrelin and hypoglycemia, the latter of which is similar to the life-threatening, fasting-induced hypoglycemia observed in infants treated with beta blockers. These findings highlight the critical functions of ghrelin in preventing hypoglycemia and promoting survival during severe caloric restriction and the requirement for ghrelin cell-expressed β1ARs in these processes. Moreover, these results indicate a potential role for ghrelin in mediating beta blocker-associated hypoglycemia in susceptible individuals, such as young children.

  12. Glutamine deficiency induces DNA alkylation damage and sensitizes cancer cells to alkylating agents through inhibition of ALKBH enzymes.

    Science.gov (United States)

    Tran, Thai Q; Ishak Gabra, Mari B; Lowman, Xazmin H; Yang, Ying; Reid, Michael A; Pan, Min; O'Connor, Timothy R; Kong, Mei

    2017-11-01

    Driven by oncogenic signaling, glutamine addiction exhibited by cancer cells often leads to severe glutamine depletion in solid tumors. Despite this nutritional environment that tumor cells often experience, the effect of glutamine deficiency on cellular responses to DNA damage and chemotherapeutic treatment remains unclear. Here, we show that glutamine deficiency, through the reduction of alpha-ketoglutarate, inhibits the AlkB homolog (ALKBH) enzymes activity and induces DNA alkylation damage. As a result, glutamine deprivation or glutaminase inhibitor treatment triggers DNA damage accumulation independent of cell death. In addition, low glutamine-induced DNA damage is abolished in ALKBH deficient cells. Importantly, we show that glutaminase inhibitors, 6-Diazo-5-oxo-L-norleucine (DON) or CB-839, hypersensitize cancer cells to alkylating agents both in vitro and in vivo. Together, the crosstalk between glutamine metabolism and the DNA repair pathway identified in this study highlights a potential role of metabolic stress in genomic instability and therapeutic response in cancer.

  13. Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse

    OpenAIRE

    Fretz, Jackie A.; Nelson, Tracy; Xi, Yougen; Adams, Douglas J.; Rosen, Clifford J.; Horowitz, Mark C.

    2010-01-01

    We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1−/− mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1−/− mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regio...

  14. Investigating Nutritional Deficiencies in a Group of Patients 3 Years Post Laparoscopic Sleeve Gastrectomy.

    Science.gov (United States)

    Zarshenas, Nazy; Nacher, Maria; Loi, Ken W; Jorgensen, John O

    2016-12-01

    Laparoscopic sleeve gastrectomy (LSG) as a single-stage procedure has shown to be effective in achieving significant weight loss and resolving obesity-related co-morbidities. However, its nutrition consequences have not been extensively explored. This study aims to investigate weight loss and evolution of nutritional deficiencies in a group of patients 3 years post LSG. Retrospective data of a group of patients, 3 years following LSG as a stand-alone procedure was collected. Data included anthropometry, nutritional markers (hemoglobin, iron studies, folate, calcium, iPTH, vitamins D, and B 12 ), and compliancy with supplementations. Ninety-one patients (male/female; 28:63), aged 51.9 ± 11.4 years with a BMI of 42.8 ± 6.1 kg/m 2 were identified to be 3 years post LSG. Percentage of weight loss at 1 and 3 years post-operatively was 29.8 ± 7.0 and 25.9 ± 8.8 %, respectively. Pre-operatively, the abnormalities included low hemoglobin (4 %), ferritin (6 %), vitamin B 12 (1 %), vitamin D (46 %), and elevated iPTH (25 %). At 3 years post-operatively, the abnormal laboratory values included low hemoglobin (14 % females, P = 0.021), ferritin (24 %, P = 0.011), vitamin D (20 %, P = 0.018), and elevated iPTH (17 %, P = 0.010). Compliancy with multivitamin supplementation was noted in 66 % of patients. In these patients, LSG resulted in pronounced weight loss at 1 year post-operatively, and most of this was maintained at 3 years. Nutritional deficiencies are prevalent among patients prior to bariatric surgery. These deficiencies may persist or exacerbate post-operatively. Routine nutrition monitoring and supplementations are essential to prevent and treat these deficiencies.

  15. Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Meredith B., E-mail: mbauman7@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Tomiya, Noboru, E-mail: ntomiya1@jhu.edu [Department of Biology, Johns Hopkins University, 3400 North Charles Street, Mudd Hall 104A, Baltimore, MD 21218 (United States); Betenbaugh, Michael J., E-mail: beten@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Krag, Sharon S., E-mail: skrag@jhsph.edu [Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 (United States)

    2010-04-23

    Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man{sub 5}GlcNAc{sub 2}-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man{sub 9}GlcNAc{sub 2}-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man{sub 5}GlcNAc{sub 2}-PP-Dol through Glc{sub 1}Man{sub 9}GlcNAc{sub 2}-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

  16. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    B Akshaya Srikanth

    2012-01-01

    Full Text Available To estimate the incidence of adverse drug reactions (ADRs in Human immune deficiency virus (HIV patients on highly active antiretroviral therapy (HAART. To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%. The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52% was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm 3 with comorbid conditions.

  17. MiR-133 is Involved in Estrogen Deficiency-Induced Osteoporosis through Modulating Osteogenic Differentiation of Mesenchymal Stem Cells.

    Science.gov (United States)

    Lv, Hao; Sun, Yujie; Zhang, Yuchen

    2015-05-27

    MiR-133 expression is dysregulated in postmenopausal osteoporosis. However, its role in postmenopausal osteoporosis is still not well understood. In the current study, we explore how estrogen deficiency affects miR-133 expression and how miR-133 is involved in osteogenic differentiation of mesenchymal stem cells (MSCs). qRT-PCR analysis was performed to assess miR-133 expression in MSCs isolated from bone marrow of an ovariectomized (OVX) animal model and postmenopausal osteoporosis patients (PMOP) and their corresponding controls. The binding between miR-133 and predicted target SLC39A1 was verified using dual luciferase assay and Western blot analysis. The effect of miR-133 and SLC39A1 on osteogenic differentiation of MSCs was assessed through measuring alkaline phosphatase (ALP), mineralization nodules, and osteoblast-specific genes Runx2 and Osterix expression. miR-133 expression is significantly enhanced as a result of estrogen deficiency. Its overexpression is negatively correlated to osteogenic differentiation of hMSCs. SLC39A1 showed an inverse expression trend to miR-133 during the differentiation. miR-133 can directly target 3'UTR of SLC39A1 and thereby modulate its expression in hMSCs. The miR-133-SLC39A1 axis might play an important role in osteogenic differentiation of hMSCs. SLC39A1 can promote ALP activity and formation of mineralization nodules. In addition, SLC39A1 expression level is also positively correlated with RUNX2 and Osterix. Estrogen deficiency is associated with miR-133 overexpression. MiR-133 can induce postmenopausal osteoporosis by weakening osteogenic differentiation of hMSCs, at least partly through repressing SLC39A1 expression.

  18. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation

    International Nuclear Information System (INIS)

    Fernandez, Carlos; Lobo, Maria del Val T.; Gomez-Coronado, Diego; Lasuncion, Miguel A.

    2004-01-01

    As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14α-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells

  19. Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, Taisuke [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Nagamatsu, Go, E-mail: gonag@sc.itc.keio.ac.jp [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kosaka, Takeo [Department of Urology, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Takubo, Keiyo [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan); Hotta, Akitsu [Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Department of Reprogramming Science, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto (Japan); Ellis, James [Ontario Human iPS Cell Facility, Molecular Genetics, University of Toronto, Developmental and Stem Cell Biology, SickKids, Toronto, Canada MG1L7 (Canada); Suda, Toshio, E-mail: sudato@sc.itc.keio.ac.jp [Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582 (Japan)

    2011-04-08

    Highlights: {yields} iPS cells were induced with a fluorescence monitoring system. {yields} ATM-deficient tail-tip fibroblasts exhibited quite a low reprogramming efficiency. {yields} iPS cells obtained from ATM-deficient cells had pluripotent cell characteristics. {yields} ATM-deficient iPS cells had abnormal chromosomes, which were accumulated in culture. -- Abstract: During cell division, one of the major features of somatic cell reprogramming by defined factors, cells are potentially exposed to DNA damage. Inactivation of the tumor suppressor gene p53 raised reprogramming efficiency but resulted in an increased number of abnormal chromosomes in established iPS cells. Ataxia-telangiectasia mutated (ATM), which is critical in the cellular response to DNA double-strand breaks, may also play an important role during reprogramming. To clarify the function of ATM in somatic cell reprogramming, we investigated reprogramming in ATM-deficient (ATM-KO) tail-tip fibroblasts (TTFs). Although reprogramming efficiency was greatly reduced in ATM-KO TTFs, ATM-KO iPS cells were successfully generated and showed the same proliferation activity as WT iPS cells. ATM-KO iPS cells had a gene expression profile similar to ES cells and WT iPS cells, and had the capacity to differentiate into all three germ layers. On the other hand, ATM-KO iPS cells accumulated abnormal genome structures upon continuous passages. Even with the abnormal karyotype, ATM-KO iPS cells retained pluripotent cell characteristics for at least 20 passages. These data indicate that ATM does participate in the reprogramming process, although its role is not essential.

  20. Identification of a novel mutation in an Indian patient with CAII deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Shivaprasad C

    2010-01-01

    Full Text Available Carbonic anhydrase II (CAII deficiency syndrome characterized by osteopetrosis (OP, renal tubular acidosis (RTA, and cerebral calcifications is caused by mutations in the carbonic anhydrase 2 (CA2 gene. Severity of this disorder varies depending on the nature of the mutation and its effect on the protein. We present here, the clinical and radiographic details along with, results of mutational analysis of the CA2 gene in an individual clinically diagnosed with renal tubular acidosis, osteopetrosis and mental retardation and his family members to establish genotype-phenotype correlation. A novel homozygous deletion mutation c.251delT was seen in the patient resulting in a frameshift and a premature stop codon at amino acid position 90 generating a truncated protein leading to a complete loss of function and a consequential deficiency of the enzyme making this a pathogenic mutation. Confirmation of clinical diagnosis by molecular methods is essential as the clinical features of the CAII deficiency syndrome are similar to other forms of OP but the treatment modalities are different. Genetic confirmation of the diagnosis at an early age leads to the timely institution of therapy improving the growth potential, reduces other complications like fractures, and aids in providing prenatal testing and genetic counseling to the parents planning a pregnancy.

  1. Porto-pulmonary hypertension exacerbated by platelet transfusion in a patient with ADAMTS13 deficiency.

    Science.gov (United States)

    Elias, Joshua E; Mackie, Ian; Eapen, Chundamannil E; Chu, Patrick; Shaw, Jean C; Elias, Elwyn

    2013-04-01

    We propose that porto-pulmonary hypertension (PPH) may arise as a consequence of deficiency of ADAMTS13 (a plasma metalloprotease that regulates von Willebrand factor size and reduces its platelet adhesive activity) and provide a clinical case history to support our hypothesis. A patient with non-cirrhotic intrahepatic portal hypertension (NCIPH), ulcerative colitis and celiac disease developed symptoms of PPH, which had advanced beyond levels which would have made her an eligible candidate for liver transplantation (mean pulmonary artery pressure (PAP) 49 mm Hg). She was known to have severe ADAMTS13 deficiency, which we considered to be causative of, or contributory to her NCIPH. We postulated that increasing porto-systemic shunting associated with advancing portal hypertension would make the next encountered vascular bed, the lung, susceptible to the pathogenic process that was previously confined to the portal system, with pulmonary hypertension as its consequence. Her pulmonary artery pressures fell significantly during the next year on weekly replacement of plasma ADAMTS13 by infusions of fresh frozen plasma and conventional drug treatment of her pulmonary hypertension. Her pulmonary artery pressures had fallen to acceptable levels when, in response to platelet infusion, it rose precipitously and dangerously. The sequence strongly supports our hypothesis that PPH is a consequence of ADAMTS13 deficiency and is caused by platelet deposition in afferent pulmonary vessels. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Mitochondrial alterations in PINK1 deficient cells are influenced by calcineurin-dependent dephosphorylation of dynamin-related protein 1.

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    Anna Sandebring

    2009-05-01

    Full Text Available PTEN-induced novel kinase 1 (PINK1 mutations are associated with autosomal recessive parkinsonism. Previous studies have shown that PINK1 influences both mitochondrial function and morphology although it is not clearly established which of these are primary events and which are secondary. Here, we describe a novel mechanism linking mitochondrial dysfunction and alterations in mitochondrial morphology related to PINK1. Cell lines were generated by stably transducing human dopaminergic M17 cells with lentiviral constructs that increased or knocked down PINK1. As in previous studies, PINK1 deficient cells have lower mitochondrial membrane potential and are more sensitive to the toxic effects of mitochondrial complex I inhibitors. We also show that wild-type PINK1, but not recessive mutant or kinase dead versions, protects against rotenone-induced mitochondrial fragmentation whereas PINK1 deficient cells show lower mitochondrial connectivity. Expression of dynamin-related protein 1 (Drp1 exaggerates PINK1 deficiency phenotypes and Drp1 RNAi rescues them. We also show that Drp1 is dephosphorylated in PINK1 deficient cells due to activation of the calcium-dependent phosphatase calcineurin. Accordingly, the calcineurin inhibitor FK506 blocks both Drp1 dephosphorylation and loss of mitochondrial integrity in PINK1 deficient cells but does not fully rescue mitochondrial membrane potential. We propose that alterations in mitochondrial connectivity in this system are secondary to functional effects on mitochondrial membrane potential.

  3. Avascular Necrosis in the Contralateral Hip in Patients With Congenital Femoral Deficiency: A Report of 3 Cases.

    Science.gov (United States)

    Brown, Timothy S; Wimberly, Robert L; Birch, John G

    2017-01-01

    Congenital femoral deficiency is an uncommon clinical entity. We report 3 patients who developed avascular necrosis of the hip in the long (normal) leg during longitudinal observation and/or treatment of congenital femoral deficiency. Patients were identified in limb length discrepancy clinic and their charts were retrospectively reviewed for clinical and radiographic data collection. We describe the occurrence of idiopathic avascular necrosis in the normal limb in patients being followed for limb length discrepancy. Although no conclusion could be drawn about the etiology of the avascular necrosis, we describe a previously undocumented relationship between congenital femoral deficiency and avascular necrosis in the contralateral hip. This occurred in our congenital femoral deficiency population at a rate higher than expected compared with published incidences of avascular necrosis of the hip in children. Level IV-case series.

  4. Extreme Beta-Cell Deficiency in Pancreata of Dogs with Canine Diabetes

    Science.gov (United States)

    Shields, Emily J.; Lam, Carol J.; Cox, Aaron R.; Rankin, Matthew M.; Van Winkle, Thomas J.; Hess, Rebecka S.; Kushner, Jake A.

    2015-01-01

    The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes. PMID:26057531

  5. Extreme Beta-Cell Deficiency in Pancreata of Dogs with Canine Diabetes.

    Directory of Open Access Journals (Sweden)

    Emily J Shields

    Full Text Available The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes.

  6. Extreme Beta-Cell Deficiency in Pancreata of Dogs with Canine Diabetes.

    Science.gov (United States)

    Shields, Emily J; Lam, Carol J; Cox, Aaron R; Rankin, Matthew M; Van Winkle, Thomas J; Hess, Rebecka S; Kushner, Jake A

    2015-01-01

    The pathophysiology of canine diabetes remains poorly understood, in part due to enigmatic clinical features and the lack of detailed histopathology studies. Canine diabetes, similar to human type 1 diabetes, is frequently associated with diabetic ketoacidosis at onset or after insulin omission. However, notable differences exist. Whereas human type 1 diabetes often occurs in children, canine diabetes is typically described in middle age to elderly dogs. Many competing theories have been proposed regarding the underlying cause of canine diabetes, from pancreatic atrophy to chronic pancreatitis to autoimmune mediated β-cell destruction. It remains unclear to what extent β-cell loss contributes to canine diabetes, as precise quantifications of islet morphometry have not been performed. We used high-throughput microscopy and automated image processing to characterize islet histology in a large collection of pancreata of diabetic dogs. Diabetic pancreata displayed a profound reduction in β-cells and islet endocrine cells. Unlike humans, canine non-diabetic islets are largely comprised of β-cells. Very few β-cells remained in islets of diabetic dogs, even in pancreata from new onset cases. Similarly, total islet endocrine cell number was sharply reduced in diabetic dogs. No compensatory proliferation or lymphocyte infiltration was detected. The majority of pancreata had no evidence of pancreatitis. Thus, canine diabetes is associated with extreme β-cell deficiency in both new and longstanding disease. The β-cell predominant composition of canine islets and the near-total absence of β-cells in new onset elderly diabetic dogs strongly implies that similar to human type 1 diabetes, β-cell loss underlies the pathophysiology of canine diabetes.

  7. Electrospun poly(ε-caprolactone)/Ca-deficient hydroxyapatite nanohybrids: Microstructure, mechanical properties and cell response by murine embryonic stem cells

    International Nuclear Information System (INIS)

    Bianco, Alessandra; Di Federico, Erica; Moscatelli, Ilana; Camaioni, Antonella; Armentano, Ilaria; Campagnolo, Luisa; Dottori, Mariaserena; Kenny, Jose Maria; Siracusa, Gregorio; Gusmano, Gualtiero

    2009-01-01

    Nanohybrid scaffolds mimicking extracellular matrix are promising experimental models to study stem cell behaviour, in terms of adhesion and proliferation. In the present study, the structural characterization of a novel electrospun nanohybrid and the analysis of cell response by a highly sensitive cell type, embryonic stem (ES) cells, are investigated. Ca-deficient hydroxyapatite nanocrystals (d-HAp) were synthesized by precipitation. Fibrous PCL/d-HAp nanohybrids were obtained by electrospinning, d-HAp content ranging between 2 and 55 wt.%. Electrospun mats showed a non-woven architecture, average fiber size was 1.5 ±0.5 μm, porosity 80-90%, and specific surface area 16 m 2 g -1 . Up to 6.4 wt.% d-HAp content, the nanohybrids displayed comparable microstructural, mechanical and dynamo-mechanical properties. Murine ES cell response to neat PCL and to nanohybrid PCL/d-HAp (6.4 wt.%) mats was evaluated by analyzing morphological, metabolic and functional markers. Cells growing on either scaffold proliferated and maintained pluripotency markers at essentially the same rate as cells growing on standard tissue culture plates with no detectable signs of cytotoxicity, despite a lower cell adhesion at the beginning of culture. These results indicate that electrospun PCL scaffolds may provide adequate supports for murine ES cell proliferation in a pluripotent state, and that the presence of d-HAp within the mat does not interfere with their growth.

  8. Acinar cell apoptosis in Serpini2-deficient mice models pancreatic insufficiency.

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    Stacie K Loftus

    2005-09-01

    Full Text Available Pancreatic insufficiency (PI when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman-Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq, exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome

  9. Mitofusin 2 Deficiency Affects Energy Metabolism and Mitochondrial Biogenesis in MEF Cells.

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    Maria Kawalec

    Full Text Available Mitofusin 2 (Mfn2, mitochondrial outer membrane protein which is involved in rearrangement of these organelles, was first described in pathology of hypertension and diabetes, and more recently much attention is paid to its functions in Charcot-Marie-Tooth type 2A neuropathy (CMT2A. Here, cellular energy metabolism was investigated in mouse embryonic fibroblasts (MEF differing in the presence of the Mfn2 gene; control (MEFwt and with Mfn2 gene depleted MEFMfn2-/-. These two cell lines were compared in terms of various parameters characterizing mitochondrial bioenergetics. Here, we have shown that relative rate of proliferation of MEFMfn2-/- cells versus control fibroblasts depend on serum supplementation of the growth media. Moreover, MEFMfn2-/- cells exhibited significantly increased respiration rate in comparison to MEFwt, regardless of serum supplementation of the medium. This effect was correlated with increased level of mitochondrial markers (TOM20 and NAO as well as mitochondrial transcription factor A (TFAM and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α protein levels and unchanged total ATP content. Interestingly, mitochondrial DNA content in MEFMfn2-/- cells was not reduced. Fundamentally, these results are in contrast to a commonly accepted belief that mitofusin 2 deficiency inevitably results in debilitation of mitochondrial energy metabolism. However, we suggest a balance between negative metabolic consequences of mitofusin 2 deficiency and adaptive processes exemplified by increased level of PGC-1α and TFAM transcription factor which prevent an excessive depletion of mtDNA and severe impairment of cell metabolism.

  10. Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

    International Nuclear Information System (INIS)

    Desai, Shrinivas; Ganesan, Karthik; Hegde, Anaita

    2008-01-01

    Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. 1 H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

  11. Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Shrinivas [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); Ganesan, Karthik [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); University of California, San Diego, Department of Radiology, San Diego, CA (United States); Hegde, Anaita [Jaslok Hospital and Research Centre, Department of Paediatrics, Mumbai (India)

    2008-08-15

    Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. {sup 1}H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

  12. Investigation of iron deficiency in patients with congestive heart failure: A medical practice that requires greater attention.

    Science.gov (United States)

    Belmar Vega, Lara; de Francisco, Alm; Albines Fiestas, Zoila; Serrano Soto, Mara; Kislikova, María; Seras Mozas, Miguel; Unzueta, Mayte García; Arias Rodríguez, Manuel

    2016-01-01

    Iron deficiency in congestive heart failure (CHF), with or without concomitant anaemia, is associated with health-related quality of life, NYHA functional class, and exercise capacity. Prospective, randomised studies have demonstrated that correcting iron deficiency improves the quality of life and functional status of patients with CHF, including those who do not have anaemia. The aim of this study was to analyse how frequently these iron parameters are tested and thus determine the extent to which this quality improvement tool has been implemented in patients admitted with CHF. Retrospective observational study of patients from a university hospital diagnosed with CHF on admission between 01/01/2012 and 11/06/2013. Iron parameters were tested in 39% (324) of the 824 patients analysed. There was no significant difference in age between the patients whose iron was tested and those whose iron was not tested, but the difference in terms of gender was significant (P=.007). Glomerular filtration rate and haemoglobin, were significantly lower in the group of patients whose iron was tested (P<.001). The proportion of patients with anaemia, renal failure or both was significantly higher in the group of patients who had iron tests (P<.001). Of the 324 patients whose iron parameters were tested, 164 (51%) had iron deficiency. There were no differences between patients with and without iron deficiency in terms of age or gender. The iron parameters in both groups, ferritin and transferrin saturation index were significantly lower among the patients with iron deficiency (P<.001). The glomerular filtration rate values were significantly lower in patients with no iron deficiency (P<.001). Significant differences were also observed between those with and without iron deficiency in the proportion of patients with renal failure (79 vs. 66%, respectively, P=.013), but not in terms of haemoglobin concentration. Congestive heart failure is very frequently associated with anaemia, iron

  13. Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats.

    Science.gov (United States)

    Abe, Ikumi; Shirato, Ken; Hashizume, Yoko; Mitsuhashi, Ryosuke; Kobayashi, Ayumu; Shiono, Chikako; Sato, Shogo; Tachiyashiki, Kaoru; Imaizumi, Kazuhiko

    2013-01-01

    Folate (vitamin B(9)) plays key roles in cell growth and proliferation through regulating the synthesis and stabilization of DNA and RNA, and its deficiency leads to lymphocytopenia and granulocytopenia. However, precisely how folate deficiency affects the distribution of a variety of white blood cell subsets, including the minor population of basophils, and the cell specificity of the effects remain unclear. Therefore, we examined the effects of a folate-deficient diet on the circulating number of lymphocyte subsets [T-lymphocytes, B-lymphocytes, and natural killer (NK) cells] and granulocyte subsets (neutrophils, eosinophils, and basophils) in rats. Rats were divided into two groups, with one receiving the folate-deficient diet (FAD group) and the other a control diet (CON group). All rats were pair-fed for 8 weeks. Plasma folate level was dramatically lower in the FAD group than in the CON group, and the level of homocysteine in the plasma, a predictor of folate deficiency was significantly higher in the FAD group than in the CON group. The number of T-lymphocytes, B-lymphocytes, and NK cells was significantly lower in the FAD group than in the CON group by 0.73-, 0.49-, and 0.70-fold, respectively, indicating that B-lymphocytes are more sensitive to folate deficiency than the other lymphocyte subsets. As expected, the number of neutrophils and eosinophils was significantly lower in the FAD group than in the CON group. However, the number of basophils, the least common type of granulocyte, showed transiently an increasing tendency in the FAD group as compared with the CON group. These results suggest that folate deficiency induces lymphocytopenia and granulocytopenia in a cell-specific manner.

  14. A deficiency of ceramide biosynthesis causes cerebellar purkinje cell neurodegeneration and lipofuscin accumulation.

    Directory of Open Access Journals (Sweden)

    Lihong Zhao

    2011-05-01

    Full Text Available Sphingolipids, lipids with a common sphingoid base (also termed long chain base backbone, play essential cellular structural and signaling functions. Alterations of sphingolipid levels have been implicated in many diseases, including neurodegenerative disorders. However, it remains largely unclear whether sphingolipid changes in these diseases are pathological events or homeostatic responses. Furthermore, how changes in sphingolipid homeostasis shape the progression of aging and neurodegeneration remains to be clarified. We identified two mouse strains, flincher (fln and toppler (to, with spontaneous recessive mutations that cause cerebellar ataxia and Purkinje cell degeneration. Positional cloning demonstrated that these mutations reside in the Lass1 gene. Lass1 encodes (dihydroceramide synthase 1 (CerS1, which is highly expressed in neurons. Both fln and to mutations caused complete loss of CerS1 catalytic activity, which resulted in a reduction in sphingolipid biosynthesis in the brain and dramatic changes in steady-state levels of sphingolipids and sphingoid bases. In addition to Purkinje cell death, deficiency of CerS1 function also induced accumulation of lipofuscin with ubiquitylated proteins in many brain regions. Our results demonstrate clearly that ceramide biosynthesis deficiency can cause neurodegeneration and suggest a novel mechanism of lipofuscin formation, a common phenomenon that occurs during normal aging and in some neurodegenerative diseases.

  15. Occurrence of GLUT1 deficiency syndrome in patients treated with ketogenic diet.

    Science.gov (United States)

    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine Cammermeyer; Selmer, Kaja Kristine

    2014-03-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a treatable metabolic encephalopathy caused by a mutation in the SLC2A1 gene. This mutation causes a compromised transport of glucose across the blood-brain barrier. The treatment of choice is ketogenic diet, with which most patients become seizure-free. At the National Centre for Epilepsy, we have, since 2005, offered treatment with ketogenic diet (KD) and modified Atkins diet (MAD) to children with difficult-to-treat epilepsy. As we believe many children with GLUT1-DS are unrecognized, the aim of this study was to search for patients with GLUT1-DS among those who had been responders (>50% reduction in seizure frequency) to KD or MAD. Of the 130 children included, 58 (44%) were defined as responders. Among these, 11 were already diagnosed with GLUT1-DS. No mutations in the SLC2A1 gene were detected in the remaining patients. However, the clinical features of these patients differed considerably from the patients diagnosed with GLUT1-DS. While 9 out of 10 patients with GLUT1-DS became seizure-free with dietary treatment, only 3 out of the 33 remaining patients were seizure-free with KD or MAD treatment. We therefore conclude that a seizure reduction of >50% following dietary treatment is not a suitable criterion for identifying patients with GLUT1-DS, as these patients generally achieve complete seizure freedom shortly after diet initiation. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Optical Coherence Tomography Assessment Before and After Vitamin Supplementation in a Patient With Vitamin A Deficiency

    OpenAIRE

    Saenz-de-Viteri, Manuel; S?daba, Luis M.

    2016-01-01

    Abstract Vitamin A is an essential fat-soluble vitamin important for the function of various body systems. In the eye, vitamin A is essential for the synthesis of visual pigments in photoreceptors. Vitamin A deficiency is a rare condition in the developed countries and might follow bariatric or intestinal bypass surgery. We present the case of a 67-year-old male that complained of visual loss and nyctalopia. Patient had bariatric surgery 15 years before for weight loss. Low serum levels of vi...

  17. Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Melisa Gorosito Serrán

    2017-11-01

    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able

  18. Irgm1-deficient mice exhibit Paneth cell abnormalities and increased susceptibility to acute intestinal inflammation.

    Science.gov (United States)

    Liu, Bo; Gulati, Ajay S; Cantillana, Viviana; Henry, Stanley C; Schmidt, Elyse A; Daniell, Xiaoju; Grossniklaus, Emily; Schoenborn, Alexi A; Sartor, R Balfour; Taylor, Gregory A

    2013-10-15

    Crohn's disease (CD) is a chronic, immune-mediated, inflammatory disorder of the intestine that has been linked to numerous susceptibility genes, including the immunity-related GTPase (IRG) M (IRGM). IRGs comprise a family of proteins known to confer resistance to intracellular infections through various mechanisms, including regulation of phagosome processing, cell motility, and autophagy. However, despite its association with CD, the role of IRGM and other IRGs in regulating intestinal inflammation is unclear. We investigated the involvement of Irgm1, an ortholog of IRGM, in the genesis of murine intestinal inflammation. After dextran sodium sulfate exposure, Irgm1-deficient [Irgm1 knockout (KO)] mice showed increased acute inflammation in the colon and ileum, with worsened clinical responses. Marked alterations of Paneth cell location and granule morphology were present in Irgm1 KO mice, even without dextran sodium sulfate exposure, and were associated with impaired mitophagy and autophagy in Irgm1 KO intestinal cells (including Paneth cells). This was manifested by frequent tubular and swollen mitochondria and increased LC3-positive autophagic structures. Interestingly, these LC3-positive structures often contained Paneth cell granules. These results suggest that Irgm1 modulates acute inflammatory responses in the mouse intestine, putatively through the regulation of gut autophagic processes, that may be pivotal for proper Paneth cell functioning.

  19. Individualizing Treatment Approaches for Epileptic Patients with Glucose Transporter Type1 (GLUT-1 Deficiency

    Directory of Open Access Journals (Sweden)

    Armond Daci

    2018-01-01

    Full Text Available Monogenic and polygenic mutations are important contributors in patients suffering from epilepsy, including metabolic epilepsies which are inborn errors of metabolism with a good respond to specific dietetic treatments. Heterozygous variation in solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1 and mutations of the GLUT1/SLC2A2 gene results in the failure of glucose transport, which is related with a glucose type-1 transporter (GLUT1 deficiency syndrome (GLUT1DS. GLUT1 deficiency syndrome is a treatable disorder of glucose transport into the brain caused by a variety of mutations in the SLC2A1 gene which are the cause of different neurological disorders also with different types of epilepsy and related clinical phenotypes. Since patients continue to experience seizures due to a pharmacoresistance, an early clinical diagnosis associated with specific genetic testing in SLC2A1 pathogenic variants in clinical phenotypes could predict pure drug response and might improve safety and efficacy of treatment with the initiation of an alternative energy source including ketogenic or analog diets in such patients providing individualized strategy approaches.

  20. Deficient mismatch repair andRASmutation in colorectal carcinoma patients: a retrospective study in Eastern China.

    Science.gov (United States)

    Zhang, Xiangyan; Ran, Wenwen; Wu, Jie; Li, Hong; Liu, Huamin; Wang, Lili; Xiao, Yujing; Wang, Xiaonan; Li, Yujun; Xing, Xiaoming

    2018-01-01

    To investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma. Clinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymerase chain reaction. Correlations of mismatch repair status and RAS mutation status with clinicopathological characteristics and disease survival were determined. The overall percentage of dMMR was 15.18% (121/797). The proportion of dMMR was higher in patients mismatch repair was also associated with mucinous production ( p  mismatch repair status and RAS mutation reflects the specific clinicopathological characteristics of colorectal carcinoma.

  1. STK11/LKB1 deficiency promotes neutrophil recruitment and proinflammatory cytokine production to suppress T cell activity in the lung tumor microenvironment

    Science.gov (United States)

    Koyama, Shohei; Akbay, Esra A.; Li, Yvonne Y.; Aref, Amir R.; Skoulidis, Ferdinandos; Herter-Sprie, Grit S.; Buczkowski, Kevin A.; Liu, Yan; Awad, Mark M.; Denning, Warren L.; Diao, Lixia; Wang, Jing; Parra-Cuentas, Edwin R.; Wistuba, Ignacio I.; Soucheray, Margaret; Thai, Tran C.; Asahina, Hajime; Kitajima, Shunsuke; Altabef, Abigail; Cavanaugh, Jillian D.; Rhee, Kevin; Gao, Peng; Zhang, Haikuo; Fecci, Peter E.; Shimamura, Takeshi; Hellmann, Matthew D.; Heymach, John V.; Hodi, F. Stephen; Freeman, Gordon J.; Barbie, David A.; Dranoff, Glenn; Hammerman, Peter S.; Wong, Kwok-Kin

    2016-01-01

    STK11/LKB1 is among the most commonly inactivated tumor suppressors in non-small cell lung cancer (NSCLC), especially in tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining the effectiveness of immunotherapies, but it is unclear whether inactivation of tumor suppressor genes such as STK11/LKB1 exert similar effects. In this study, we investigated the consequences of STK11/LKB1 loss on the immune microenvironment in a mouse model of KRAS-driven NSCLC. Genetic ablation of STK11/LKB1 resulted in accumulation of neutrophils with T cell suppressive effects, along with a corresponding increase in the expression of T cell exhaustion markers and tumor-promoting cytokines. The number of tumor-infiltrating lymphocytes was also reduced in LKB1-deficient mouse and human tumors. Furthermore, STK11/LKB1 inactivating mutations were associated with reduced expression of PD-1 ligand PD-L1 in mouse and patient tumors as well as in tumor-derived cell lines. Consistent with these results, PD-1 targeting antibodies were ineffective against Lkb1-deficient tumors. In contrast, treating Lkb1-deficient mice with an IL-6 neutralizing antibody or a neutrophil-depleting antibody yielded therapeutic benefits associated with reduced neutrophil accumulation and proinflammatory cytokine expression. Our findings illustrate how tumor suppressor mutations can modulate the immune milieu of the tumor microenvironment, and they offer specific implications for addressing STK11/LKB1 mutated tumors with PD-1 targeting antibody therapies. PMID:26833127

  2. Mutation R96W in cytochrome P450c17 gene causes combined 17{alpha}-hydroxylase/17-20-lyase deficiency in two french canadian patients

    Energy Technology Data Exchange (ETDEWEB)

    LaFlamme, N.; Leblanc, J.F.; Mailloux, J. [Laval Univ., Quebec (Canada)

    1996-01-01

    Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn children. In contrast to CAH caused by 21{alpha}-hydroxylase and 11{beta}-hydroxylase deficiencies, which impairs steroid formation in the adrenal exclusively, 17{alpha}-hydroxylase/17,20-lyase deficiency impairs steroid biosynthesis in the adrenals and gonads. The sequence of CYP17 gene was determined by direct sequencing of asymmetric PCR products in two French-Canadian 46,XY pseudohermaphrodite siblings suffering from combined 17{alpha}-hydroxylase/17,20-lyase deficiency. The two patients are homozygous for the novel missense mutation R96W caused by a C to T transition converting codon Arg{sup 96} (CGG) into a Trp (TGG) in exon 1. Both parents are heterozygous for this missense mutation. We assessed the effect of the R96W mutation on 17{alpha}-hydroxylase/17,20-lyase activity by analysis of mutant enzyme, generated by site-directed mutagenesis, expressed in COS-1 cells. The presence of R96W substitution almost completely abolished the activity of the mutant protein. The present findings provide a molecular explanation for the signs and symptoms of combined 17 {alpha}-hydroxylase/17,20-lyase deficiency in these two patients and provide useful information on the structure-activity relationships of the P450c17 enzyme. 31 refs., 4 figs., 1 tab.

  3. ANALYSIS OF BILIARY CHOLESTEROL LEVELS IN IRON-DEFICIENT PATIENTS OPERATED FOR GALLSTONE DISEASE

    Directory of Open Access Journals (Sweden)

    R. Kannan

    2017-01-01

    Full Text Available BACKGROUND Gallstone disease is a common gastrointestinal problem in day-to-day practice. The old concept that a typical gallstone sufferer is fat, fertile, flatulent female of 50. This is partially true as the disease has been found in women soon after their first delivery who are thin and underweight and in males also. Conditions that favour the formation of cholesterol gallstones are super saturation of bile with cholesterol, kinetically favourable nucleation and presence of cholesterol crystals in the gallbladder long enough to agglomerate into a stone. Recent studies have defined the role of trace elements (Fe, Ca, Zn and Cu and defective pH in the formation of gallstones. The aim of the study is to determine the association of iron deficiency in super saturation of bile. This cross-sectional study of 50 patients was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. Biliary cholesterol and serum cholesterol were compared in iron deficient and non-iron deficient patients having gallstones. A low serum iron level is a factor in bile super saturation with respect to cholesterol leading to gallstone formation. MATERIALS AND METHODS This study was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. 50 patients suffering from cholelithiasis confirmed by USG were divided into two groups based on serum iron values. Group A consists of patients with normal serum iron (non-anaemic and Group B of patients with less than normal serum iron (anaemic. RESULTS Serum total cholesterol of the patients of cholelithiasis was not different among groups categorised based on serum iron levels. There were no significant variations in the serum cholesterol contents of both the groups. Also, there was no significant variation of the above parameter in the male and female patients. CONCLUSION Though, it is difficult to draw a causal

  4. [Effect of SET deficiency on the trichloroethylene-induced alteration of cell proliferation and cell apoptosis and DNA methylation in human hepatic L-02 cells].

    Science.gov (United States)

    Xie, G S; Liu, J J; Hong, W X; Zhang, H; Sun, Y; Zhu, W G

    2016-03-20

    To compare the trichloroethylene (TCE) -induced alteration in cell proliferation, cell apoptosis, histone deacetylase activity and expression levels in human hepatic L-02 cells (L-02 cells) and SET deficient cells, and reveal the TCE-induced effect in histone modification and the role of SET on epigenetic pathway. The L-02 cells and preestablished SET deficient cells were treated with different TCE concentrations. For the changes of cell proliferation level and apoptosis rate, The L-02 cells and SET deficiency cells without TCE treatment were served as the control group, the TCE treatment was in the concentration of 2.0 and 8.0 mmol/L for 24 h. For histone deacetylase activity and expression levels, the TCE treatment was in the concentration of 0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mmol/L for 24 h. After treatment with TCE for 24 h, the cell proliferation level was significantly decreased and the apoptotic rate was significantly increased in both cell lines. When concentration of TCE were reached to 8.0 mmol/L, the difference of cell proliferation level and apoptotic rate between two groups was statistically significant (t=-4.362 for proliferation level and t=23.950 for apoptotic rate, both Pcell lines. When the TCE concentration were high than 0.50 mmol/L, compared with control group of L-02 cells, the enzymes activity were significantly increased (F=403.26, Pcells, the enzyme activity was significantly increased when TCE concentration was reached 1.00 mmol/L (F=44.01, Pcells, TCE exposure can induced a significant increased expression level of HDAC2 in TCE-treated L-02 cells (F values were 79.99, Pcells was not significant. TCE exposure can induce a significant alteration on cell proliferation, apoptotic rate and, the activity and expression on histone deacetylases. SET deficiency can attenuate the TCE-induced alteration in histone modification in L-02 cells. Our results indicated that SET is involved in the mechanism of TCE-induced cytotoxicity and epigenetic

  5. Heart failure in patients with kidney disease and iron deficiency: The role of iron therapy

    Directory of Open Access Journals (Sweden)

    Aleix Cases Amenós

    2017-11-01

    Full Text Available Chronic kidney disease and anaemia are common in heart failure (HF and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a post hoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Resumen: La enfermedad renal crónica y la anemia son frecuentes en la insuficiencia cardíaca (IC y su presencia se asocia con un peor pronóstico en estos pacientes. La ferropenia es frecuente en pacientes con IC y aumenta el riesgo de morbimortalidad, independientemente de la presencia o no de anemia. Mientras el tratamiento de la anemia con agentes estimuladores de la eritropoyesis en pacientes con IC no ha demostrado un beneficio sobre la morbimortalidad, el tratamiento con hierro intravenoso (iv en pacientes con IC y fracción de eyección disminuida y déficit de hierro se asocia con una mejoría clínica. Además, en un análisis post hoc de un ensayo clínico, la ferroterapia mejoró la función renal en pacientes con IC y

  6. Histone deacetylase inhibitor upregulates peroxisomal fatty acid oxidation and inhibits apoptotic cell death in abcd1-deficient glial cells.

    Science.gov (United States)

    Singh, Jaspreet; Khan, Mushfiquddin; Pujol, Aurora; Baarine, Mauhamad; Singh, Inderjit

    2013-01-01

    In X-ALD, mutation/deletion of ALD gene (ABCD1) and the resultant very long chain fatty acid (VLCFA) derangement has dramatically opposing effects in astrocytes and oligodendrocytes. While loss of Abcd1 in astrocytes produces a robust inflammatory response, the oligodendrocytes undergo cell death leading to demyelination in X-linked adrenoleukodystrophy (X-ALD). The mechanisms of these distinct pathways in the two cell types are not well understood. Here, we investigated the effects of Abcd1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oligodendrocytes. Loss of Abcd1 inhibited peroxisomal β-oxidation activity and increased expression of VLCFA synthesizing enzymes, elongase of very long chain fatty acids (ELOVLs) (1 and 3) in both cell types. However, higher induction of ELOVL's in Abcd1-deficient B12 oligodendrocytes than astrocytes suggests that ELOVL pathway may play a prominent role in oligodendrocytes in X-ALD. While astrocytes are able to maintain the cellular homeostasis of anti-apoptotic proteins, Abcd1-deletion in B12 oligodendrocytes downregulated the anti-apototic (Bcl-2 and Bcl-xL) and cell