26 research outputs found
Innate and adaptive immune responses in viral and chronic inflammatory diseases
No full textIn this thesis I address some important questions regarding innate and adaptiveimmune responses in different human diseases. We analysed two distinctconditions: chronic autoimmune inflammation, specifically SLE, and chronic viralinfection, represented by herpes simplex virus (HSV). The role of differentcomponents of the immune system were addressed, ranging from innate factors,such as IFN-alpha and NK cells, to the adaptive immune system, represented by Tcells.The results are discussed with respect to the various possible levels ofinteraction between the innate and the adaptive immune systems.We first focused on a specific subset of NK cells, CD56bright NK cells, which isnormally found in lymphoid tissue and at sites of inflammation and which, uponactivation, has the capacity to produce large amounts of cytokines. CD56bright NKcells are often discussed in relation to their possible role in shaping adaptiveimmune responses. The proportion of CD56bright NK cells was significantlyincreased in blood in subjects affected by SLE. This finding was not dependent ondisease activity and may be due to increased levels of IFN-alpha, a typical hallmarkof SLE patients.We then investigated several aspects of herpes virus infections. We describe apossible role for the activating NK cell receptor NKG2D in the immune responseagainst HSV1 infection. We determined that HSV1 has the ability to downregulatethe cell surface expression of NKG2D ligands of infected cells. We also observedthat NK cells from patients affected by recurrent HSV1 manifestations haveslightly increased levels of expression of NKG2D on blood NK cells during theacute phase of viral reactivation. In a prospective clinical study of patients withHSV genital infection, we observed that low specific T-cell responses against HSV-antigens during primary HSV1 and 2 infection predict a high frequency of clinicalrecurrences. Finally we examined the immune response of patients affected byrecurrent meningitis caused by HSV2 infection. During asymptomatic periods,these patients showed elevated expression of TLR3 and TLR9, elevated IFN-alphaproduction to certain stimuli and elevated specific T-cell responses when comparedto patients with recurrent genital infection and to healthy seropositive donors. Inaddition, there were qualitative differences in their T-cell cytokine profile. Weconclude that HSV2 meningitis is likely not a consequence of an impaired antiviralinnate or adaptive immune sponse at the systemic level.List of scientific papersI. Schepis D, Gunnarsson I, Eloranta ML, Lampa J, Jacobson SH, Kärre K, Berg L (2009). "Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus." Immunology 126(1): 140-6. Epub 2008 Jun 18 https://doi.org/10.1111/j.1365-2567.2008.02887.x II. Schepis D, DAmato M, Studahl M, Bergström T, Kärre K, Berg L (2009). "Herpes simplex virus infection downmodulates NKG2D ligand expression". [Accepted] https://doi.org/10.1111/j.1365-3083.2009.02241.x III. Franzen-Röhl E, Schepis D, Atterfelt F, Franck K, Vikström A, Liljeqvist JÅ, Bergström T, Aurelius E, Kärre K, Berg L, Gaines H (2009). "Herpes simplex virus specific T-cell response in primary infection correlate inversely with frequency of subsequent recurrences". [Manuscript]IV. Franzen-Röhl E, Schepis D, Lagrelius M, Franck K, Jones P, Liljeqvist JÅ, Bergström T, Aurelius E, Kärre K, Berg L, Gaines H (2009). "Increased cell mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis". [Manuscript]</p
Erratum: Alcoholic and nonalcoholic liver disease: Diagnostic assessment and therapeutic perspectives (BioMed Research International (2019) 2019 (8691502) DOI: 10.1155/2019/8691502)
No full textIn the article titled “Alcoholic and Nonalcoholic Liver Disease: Diagnostic Assessment and Therapeutic Perspectives” [1], the affiliation “University of Valencia, Hospital La Fe, Valencia, Spain” was incorrectly assigned to the author Dr. Marina Berenguer. The correct affiliations for this author are shown below, and they have been added as affiliations 6, 7, and 8 in the author information above: CIBER-EHD, Instituto de Salud Carlos III, Madrid, Spain Hepatology and Liver Transplantation Unit, IIS La Fe, Hospital Universitario y Politécnico La Fe, Valencia, Spain Faculty of Medicine, University of Valencia, Valencia, Spain
Viollet-le-Duc and the “restoration” of Mont Blanc
No full textThe essay, a synthesis of the Ph.D. thesis of the author, examines the study of Viollet-le-Duc on Mont Blanc, starting from the analysis of his book Le massif du Mont Blanc. The translation of the book, the study of text and illustrations, on which the research is based, was the occasion to verify some key topics on the theoretical and design activity of the French architect: observation as a tool of knowledge and drawing as verification, communication and validation of an idea. In general, the study also investigates the interest of Viollet-le-Duc in natural phenomena, in particular the attraction for mountains, which is documented by many, little-known writings, drawings and surveys. It also opens up new, fruitful reflections on the usefulness of drawing, iconographic restitution, protection and restoration of landscape. Finally, the essay underlines the unity of method in Viollet-le-Duc’s studies. He was convinced that the earth is a great building in which each part has a role. For this reason, he had the same approach both for the study of deformations of the earth’s crust and the analyses of medieval constructive techniques
Making Exercise Part of the Daily Routine
No full textA survey conducted to examine the influence of technology and sedentary activities, time management, and motivation to become more physically active.Spring 2012Accompanied by video fil
natural killer cells in active and inactive systemic lupus erythematosus
No full textNatural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.</p
UNRESECTABLE HEPATOCELLULAR CARCINOMA:META-ANALYSIS OD ARTERIAL EMBOLIZATION
No full text. Radiology. 2002 Jul;224(1):47-54.
Transarterial chemoembolization for unresectable hepatocellular carcinoma:
meta-analysis of randomized controlled trials.
Cammà C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P,
Craxì A, Cottone M.
National Council of Research, Istituto Metodologie Diagnostiche Avanzate,
Palermo, Italy. [email protected]
Comment in
Radiology. 2003 May;227(2):611-2; author reply 612-3.
Radiology. 2004 Jan;230(1):300-1; author reply 301-2.
PURPOSE: To review the available evidence of chemoembolization for unresectable
hepatocellular carcinoma (HCC).
MATERIALS AND METHODS: Computerized bibliographic searches with MEDLINE and
CANCERLIT databases from 1980 through 2000 were supplemented with manual
searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma,"
"randomized controlled trial [RCT]," and "chemoembolization." Studies were
included if patients with unresectable HCC were enrolled and if they were RCTs in
which chemoembolization was compared with nonactive treatment (five RCTs) or if
different transarterial modalities of therapy (13 RCTs) were compared. Data were
extracted from each RCT according to the intention-to-treat method. Five of the
RCTs with a nonactive treatment arm were combined by using the random-effects
model, whereas all 18 RCTs were pooled from meta-regression analysis.
RESULTS: Chemoembolization significantly reduced the overall 2-year mortality
rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive
treatment. Analysis of comparative RCTs helped to predict that overall mortality
was significantly lower in patients treated with transarterial embolization (TAE)
than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI:
0.53, 0.98; P =.039) and that there is no evidence that transarterial
chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79,
1.27; P =.95), which suggests that the addition of an anticancer drug did not
improve the therapeutic benefit.
CONCLUSION: In patients with unresectable HCC, chemoembolization significantly
improved the overall 2-year survival compared with nonactive treatment, but the
magnitude of the benefit is relatively small
Multiple Polymorphisms Affect Expression and Function of the Neuropeptide S Receptor (NPSR1)
No full textPeer reviewe
Increased Cell-Mediated Immune Responses in Patients with Recurrent Herpes Simplex Virus Type 2 Meningitis
No full textABSTRACTThe clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.</jats:p
