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91.
Barral P Eckl-Dorna J Harwood NE De Santo C Salio M Illarionov P Besra GS Cerundolo V Batista FD 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(24):8345-8350
Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid. Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo. 相似文献
92.
Matrone C Ciotti MT Mercanti D Marolda R Calissano P 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(35):13139-13144
Here, we report that interruption of NGF or BDNF signaling in hippocampal neurons rapidly activates the amyloidogenic pathway and causes neuronal apoptotic death. These events are associated with an early intracellular accumulation of PS1 N-terminal catalytic subunits and of APP C-terminal fragments and a progressive accumulation of intra- and extracellular Aβ aggregates partly released into the culture medium. The released pool of Aβ induces an increase of APP and PS1 holoprotein levels, creating a feed-forward toxic loop that might also cause the death of healthy neurons. These events are mimicked by exogenously added Aβ and are prevented by exposure to β- and γ-secretase inhibitors and by antibodies directed against Aβ peptides. The same cultured neurons deprived of serum die, but APP and PS1 overexpression does not occur, Aβ production is undetectable, and cell death is not inhibited by anti-Aβ antibodies, suggesting that hippocampal amyloidogenesis is not a simple consequence of an apoptotic trigger but is due to interruption of neurotrophic signaling. 相似文献
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Chiara Baldini Andrea Delle Sedie Nicoletta Luciano Pasquale Pepe Francesco Ferro Rosaria Talarico Chiara Tani Marta Mosca 《Rheumatology international》2014,34(8):1159-1164
Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH-vitamin D deficiency seems to be involved in the development and severity of several autoimmune diseases. To date, contrasting data have been reported regarding the presence of hypovitaminosis D in primary Sjögren’s syndrome (pSS). To assess the prevalence of hypovitaminosis D in pSS at an early stage of the disease and to evaluate its impact on pSS clinical manifestations and disease activity, unselected consecutive subjects with recent onset dry mouth and/or dry eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria) were prospectively included in the study. The levels of 25[OH]-D3 were measured by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20–30 ng/ml, respectively, and their frequencies were investigated in pSS patients and controls. The levels of 25[OH]-D3 were also correlated with patients’ demographic, clinical, and serologic features. Seventy-six consecutive females were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining 46/76 patients represented the control group. No statistical differences were found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20 ng/ml (IQR 9.3–26)] and controls [median levels = 22.5 ng/ml (IQR 15.6–33)]. In particular, the frequency of 25[OH]-D3 severe deficiency was not significantly different in patients with pSS when compared to controls (23 vs. 17.4 %, p value = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia was significantly associated with 25[OH]-D3 severe deficiency, being documented in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any further association or correlation between hypovitaminosis D and pSS glandular and extra-glandular features. Although the role of hypovitaminosis D in pSS pathogenesis remains controversial, the results of this study encourage the assessment of vitamin D in specific pSS subsets that could mostly benefit from a supplementation. 相似文献
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97.
Michelle W. Ng Julie Angerosa Igor E. Konstantinov Michael M. Cheung Salvatore Pepe 《Clinical and experimental pharmacology & physiology》2019,46(11):995-1000
Remote ischaemic preconditioning (RIPC) has been employed as a non‐invasive protective intervention against myocardial ischaemia–reperfusion injury in animal studies. However, the underlying mechanisms are incompletely defined in humans and its clinical efficacy has been inconclusive. As advanced age, disease, and drugs may confound RIPC mechanisms in patients, our aim is to measure whether RIPC evokes release of adenosine, bradykinin, met‐enkephalin, nitric oxide, and apolipoproteins in healthy young adults. Healthy subjects (n = 18, 9 males, 23 ± 1.5 years old; 9 females, 23 ± 1.8 years old) participated after informed consent. RIPC was applied using a blood pressure cuff to the dominant arms for four cycles of 5‐minute cuff inflation (ischaemia) and 5‐minute cuff deflation (reperfusion). Blood was sampled at baseline and immediately after the final cuff deflation (Post‐RIPC). Baseline and Post‐RIPC plasma levels of adenosine, bradykinin, met‐enkephalin, apolipoprotein A‐1 (ApoA‐1), apolipoprotein D (ApoD), and nitric oxide (as nitrite) were measured via ELISA and high‐performance liquid chromatography. Mean (±SD) baseline levels of adenosine, bradykinin, met‐enkephalin, ApoA‐1, ApoD, and nitrite in healthy young adults were 13.8 ± 6.5 ng/mL, 2.6 ± 1.9 μg/mL, 594.1 ± 197.4 pg/mL, 3.0 ± 0.7 mg/mL, 22.2 ± 4.0 μg/mL, and 49.8 ± 13.4 nmol/L, respectively. Post‐RIPC adenosine and nitrite levels increased (59.5 ± 37.9%, P < .0001; 32.2 ± 19.5%, P < .0001), whereas met‐enkephalin and ApoD levels marginally decreased (5.3 ± 14.0%, P = .04; 10.8 ± 20.5%, P = .04). Post‐RIPC levels were not influenced by sex, age, blood pressure, waist circumference, or BMI. RIPC produces increased levels of adenosine and nitrites, and decreased met‐enkephalin and ApoD in the plasma of young healthy adults. 相似文献
98.
Zampella Emilia Acampa Wanda Assante Roberta Gaudieri Valeria Nappi Carmela Mannarino Teresa Mainolfi Ciro Gabriele Arumugam Parthiban Petretta Mario Cuocolo Alberto 《European journal of nuclear medicine and molecular imaging》2020,47(7):1698-1704
European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),... 相似文献
99.
Ahmet Ozmeric Nevres Hurriyet Aydogan Onur Kocadal Talip Kara Murad Pepe Serap Gozel 《International journal of surgery case reports》2014,5(12):1010-1013
INTRODUCTION
Synovial chondromatosis is characterized by the presence of metaplastic cartilage nodules originating from the synovia, bursa and tendon sheaths. Although it is extremely rare in the ankle joint, malignant transformation is possible. The choice of treatment is usually open surgery for excision of loose bodies and synovectomy. Limited data is available concerning arthroscopic approaches.PRESENTATION OF CASE
A 28-year-old male patient was evaluated for pain and swelling of the right ankle joint. Based on the findings of physical examination and radiographic investigations, arthroscopic surgery was performed due to ankle impingement syndrome. A diagnosis of synovial osteochondromatosis was made following the pathological survey.DISCUSSION
Synovial chondromatosis is slowly progressive and is considered to be a self-limiting situation. Treatment strategies are decided on according to the patient''s complaints, age and disease stage. Open or arthroscopic surgery. can be performed. Some advantages of arthroscopic surgery are wide visualization areas, easy access to areas difficult to reach, lower morbidity, no necessity for casting and immobilization, early rehabilitation and quick recovery period.CONCLUSION
In conclusion, arthroscopic management can be successful in selected patients with synovial osteochondromatosis localized to the ankle joint. 相似文献100.
Definition of minimal duplicated region encompassing the XIAP and STAG2 genes in the Xq25 microduplication syndrome 下载免费PDF全文
Daniela Di Benedetto Sebastiano Antonino Musumeci Emanuela Avola Antonino Alberti Serafino Buono Carmela Scuderi Lucia Grillo Ornella Galesi Angela Spalletta Mariangela Lo Giudice Daniela Luciano Mirella Vinci Sebastiano Bianca Corrado Romano Marco Fichera 《American journal of medical genetics. Part A》2014,164(8):1923-1930